Publications by authors named "Richard Chocron"

31 Publications

Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: insight from VWF/ADAMTS13 ratio imbalance.

Angiogenesis 2021 May 11. Epub 2021 May 11.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006, Paris, France.

Background: Microthrombosis is a hallmark of COVID-19. We previously described von willebrand factor (VWF) and their high molecular weight multimers (HMWMs) as potential trigger of microthrombosis.

Objectives: Investigate VWF activity with collagen-binding assay and ADAMTS13 in COVID-19.

Methods And Results: Our study enrolled 77 hospitalized COVID-19 patients including 37 suffering from a non-critical form and 40 with critical form. Plasma levels of VWF collagen-binding ability (VWF:CB) and ADAMTS13 activity (ADAMTS13:Act) were measured in the first 48 hours following admission. VWF:CB was increased in critical (631% IQR [460-704]) patients compared to non-critical patients (259% [235-330], p < 0.005). VWF:CB was significantly associated (r = 0.564, p < 0.001) with HMWMs. Moreover, median ADAMTS13:Act was lower in critical (64.8 IU/dL IQR 50.0-77.7) than non-critical patients (85.0 IU/dL IQR 75.8-94.7, p < 0.001), even if no patients displayed majors deficits. VWF:Ag-to-ADAMTS13:Act ratio was highly associated with VWF:CB (r = 0.916, p < 0.001). Moreover, VWF:CB level was highly predictive of COVID-19 in-hospital mortality as shown by the ROC curve analysis (AUC = 0.92, p < 0.0001) in which we identified a VWF:CB cut-off of 446% as providing the best predictor sensitivity-specificity balance. We confirmed this cut-off thanks to a Kaplan-Meier estimator analysis (log-rank p < 0.001) and a Cox-proportional Hazard model (HR = 49.1, 95% CI 1.81-1328.2, p = 0.021) adjusted on, BMI, C-reactive protein, and D-dimer levels.

Conclusion: VWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity.
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http://dx.doi.org/10.1007/s10456-021-09789-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111656PMC
May 2021

Association between functional status at hospital discharge and long-term survival after out-of-hospital-cardiac-arrest.

Resuscitation 2021 May 6. Epub 2021 May 6.

University of Washington, Department of Emergency Medicine, Seattle, USA; Emergency Medical Services Division, Public Health Seattle and King County, Seattle, USA. Electronic address:

Background: Out-of-hospital cardiac arrest (OHCA) causes brain injury. Functional status of survivors at hospital discharge is a core resuscitation measure, frequently using the Cerebral Performance Category (CPC) or modified Rankin Scale (mRS). Which scale better predicts long-term survival following OHCA is not known.

Methods: We evaluated long-term survival after hospital discharge in a retrospective cohort of persons resuscitated from OHCA in King County, WA from 2007 to 2015. Patients were independently assessed at discharge using both scales, leveraging the regional quality improvement registry, which records the 5-level CPC, and concurrent research studies involving the Resuscitation Outcomes Consortium, which used the 7-level mRS, taken from information in the hospital record. The risk of mortality associated with CPC and mRS categories was estimated using Kaplan-Meier survival analysis and Cox proportional hazards regression.

Results: Among 878 eligible patients discharged alive, there were 358 deaths during 9118.5 person-years of follow-up. Overall 1, 5 and 10-year survival was 84.4%, 68.5%, and 53.7% and varied according to CPC and mRS (p < 0.01 per Kaplan Meier). Compared to CPC-1, Hazard Ratio (HR) increased incrementally for CPC-2 = 1.33 (1.03-1.73), CPC-3 = 1.90 (1.37-2.65), and CPC-4 = 8.25 (5.63-12.10). Compared to mRS = 0, HR for mRS-1 = 1.02 (0.66-1.58), mRS-2 = 1.52 (1.00-2.32), mRS-3 = 1.41 (0.92-2.14), mRS-4 = 2.00 (1.37-2.97), and mRS-5 = 4.90 (3.23-7.44).

Conclusion: In OHCA survivors, CPC and mRS scales both predicted long-term survival. However mRS 0-1 and 2-3 groups did not have distinct prognoses, suggesting that a consolidated mRS score may simplify capture of relevant prognostic information for survival predictions.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.031DOI Listing
May 2021

Lupus anticoagulant single positivity at acute phase is not associated with venous thromboembolism or in-hospital mortality in COVID-19.

Arthritis Rheumatol 2021 Apr 21. Epub 2021 Apr 21.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France, Respiratory Medicine Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique - Hôpitaux de Paris-Centre (APHP-CUP), F-75015, Paris, France.

Introduction: Antiphospholipid antibodies (APA) clinical relevance in COVID-19 is controversial. We aimed to investigate the prevalence and prognostic value of conventional and non-conventional APA in COVID-19 patients.

Methods: This study was a multi-centric, prospective observational French cohort of patients hospitalized for COVID-19 suspicion.

Results: 249 patients were hospitalized for suspected COVID-19, including 154 with confirmed COVID-19 and 95 not confirmed. We found a significant increase in lupus anticoagulant (LA) positivity among COVID-19 positive patients (60.9% versus 23.7% in non-COVID19 patients, p<0.001), while prevalence of conventional (anti-cardiolipin and anti-beta-2-GP1, IgG and IgM isotypes) and non-conventional APA (IgA, anti-phosphatidylserine/prothrombin and anti-prothrombin IgG and IgM) were low in both groups. COVID-19 patients with LA positivity had higher levels of fibrinogen (6.0 IQR 5.0-7.0 versus 5.3 g/L IQR 4.3-6.4, p=0.028) and C-reactive protein (CRP, 115.5 IQR 66.0-204.8 versus 91.8 mg/L IQR 27.0-155.1, p=0.019). Univariate analysis did not show any association between LA positivity and higher risk of venous thromboembolism (VTE, OR 1.02, 95% CI 0.44-2.43, p=0.95) or in-hospital mortality (OR 1.80, 95% CI 0.70-5.05, p=0.24). Unadjusted and adjusted (to CRP, age and sex) Kaplan-Meier survival curves according to LA positivity confirmed the absence of association with VTE or in-hospital mortality (unadjusted: p=0.64 and p=0.26, respectively; adjusted: hazard ratio = 1.13 95% CI 0.48-2.60 and 1.80 95% CI 0.67-5.01).

Conclusions: COVID-19 patients have an increased prevalence of LA positivity associated with biological inflammation markers. However, positive LA at admission is not associated with VTE risk and/or in-hospital mortality.
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http://dx.doi.org/10.1002/art.41777DOI Listing
April 2021

Vaccination against COVID-19: insight from arterial and venous thrombosis occurrence using data from VigiBase.

Eur Respir J 2021 Apr 16. Epub 2021 Apr 16.

Université de Paris, Innovative Therapies in Hemostasis, INSERM, Paris, France; Pharmacovigilance Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.

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http://dx.doi.org/10.1183/13993003.00956-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051185PMC
April 2021

D-dimer at hospital admission for COVID-19 are associated with in-hospital mortality, independent of venous thromboembolism: Insights from a French multicenter cohort study.

Arch Cardiovasc Dis 2021 Mar 9. Epub 2021 Mar 9.

Université de Paris, PARCC, INSERM, 75015 Paris, France.

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimer, and increased frequency of venous thromboembolism.

Aim: To explore the association between D-dimer at admission and in-hospital mortality in patients hospitalised for COVID-19, with or without symptomatic venous thromboembolism.

Methods: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality and venous thromboembolism) of patients hospitalised for COVID-19 in medical wards were retrospectively analysed in a multicenter study in 24 French hospitals.

Results: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration>1128ng/mL as the best cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 60-69), with a sensitivity of 71.1% (95% CI 62-78) and a specificity of 55.6% (95% CI 52-58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalisation. Among 545 (47.2%) patients with D-dimer concentration>1128ng/mL at admission, 86 (15.8%) deaths occurred during hospitalisation. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration>1128ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05-4.69; P<0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31-3.4; P<0.01).

Conclusions: D-dimer concentration>1128ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalised for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalisation.
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http://dx.doi.org/10.1016/j.acvd.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942155PMC
March 2021

Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality.

J Thromb Haemost 2021 Apr 8. Epub 2021 Apr 8.

Université de Paris, PARCC, INSERM, F-75015, Paris, France.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury.

Objectives: Correlate circulating angiogenic markers VEGF-A, PlGF and FGF-2 to in-hospital mortality in COVID-19 adult patients.

Methods: Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF and FGF-2 were measured in each patient ≤48 h following admission.

Results: Study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19 of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF and FGF-2 significantly increase with the severity of the disease (p<0.001). Using a logistic regression model we found a significant association between the increase of FGF-2 or PlGF and mortality (OR 1.11, 95% CI [1.07-1.16], p<0.001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], p<0.001 for PlGF) while no association were found for VEGF-A levels. ROC curve analysis was performed and we identified PlGF above 30 pg/mL as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curves (p=0.001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer and CRP (3.23 95% CI [1.29-8.11], p=0.001).

Conclusion: Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.
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http://dx.doi.org/10.1111/jth.15339DOI Listing
April 2021

Appropriate Use of Idarucizumab for Dabigatran Reversal According to the International Society on Thrombosis and Hemostasis and French Working Group on Perioperative Hemostasis: A French Retrospective Study.

J Cardiothorac Vasc Anesth 2021 Feb 12. Epub 2021 Feb 12.

Université de Paris, Innovative Therapies in Hemostasis, INSERM; Hematology Department and Biosurgical Research Lab, (Carpentier Foundation) Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), 75015, Paris, France; F-CRIN INNOVTE, Saint-Étienne, France.

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http://dx.doi.org/10.1053/j.jvca.2021.02.029DOI Listing
February 2021

Bystander Cardiopulmonary Resuscitation Quality: Potential for Improvements in Cardiac Arrest Resuscitation.

J Am Heart Assoc 2021 Mar 4;10(6):e017930. Epub 2021 Mar 4.

University of Washington Seattle WA.

Background Bystander cardiopulmonary resuscitation (CPR) is a critical intervention to improve survival following out-of-hospital cardiac arrest. We evaluated the quality of bystander CPR and whether performance varied according to the number of bystanders or provision of telecommunicator CPR (TCPR). Methods and Results We investigated non-traumatic out-of-hospital cardiac arrest occurring in a large metropolitan emergency medical system during a 6-month period. Information about bystander care was ascertained through review of the 9-1-1 recordings in addition to emergency medical system and hospital records to determine bystander CPR status (none versus TCPR versus unassisted), the number of bystanders on-scene, and CPR performance metrics of compression fraction and compression rate. Of the 428 eligible out-of-hospital cardiac arrest, 76.4% received bystander CPR including 43.7% unassisted CPR and 56.3% TCPR; 35.2% had one bystander, 33.3% had 2 bystanders, and 31.5% had ≥3 bystanders. Overall compression fraction was 59% with a compression rate of 88 per minute. CPR differed according to TCPR status (fraction=52%, rate=87 per minute for TCPR versus fraction=69%, rate=102 for unassisted CPR, <0.05 for each comparison) and the number of bystanders (fraction=55%, rate=87 per minute for 1 bystander, fraction=59%, rate=89 for 2 bystanders, fraction=65%, rate=97 for ≥3 bystanders, test for trend <0.05 for each metric). Additional bystander actions were uncommon to include rotation of compressors (3.1%) or application of an automated external defibrillator (8.0%). Conclusions Bystander CPR quality as gauged by compression fraction and rate approached guideline goals though performance depended upon the type of CPR and number of bystanders.
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http://dx.doi.org/10.1161/JAHA.120.017930DOI Listing
March 2021

Establishing a written advice sheet to patients consulting for wound to emergency ward improves postemergency care.

Turk J Emerg Med 2021 Jan-Mar;21(1):6-13. Epub 2020 Dec 1.

Department of Emergency, Paris University, AP-HP, Georges Pompidou European Hospital, F-75015 Paris, France.

Objectives: Sutures require follow-up visits for favorable evolution. To improve postemergency wound care, we decided to include a standardized advice sheet for patients based on current recommendations. The objective is to assess its effectiveness on outpatients' compliance after being discharged from the emergency department (ED).

Methods: We performed a prospective, pre-post design trial in an ED of a teaching hospital. We included for two consecutive months all patients aged ≥16 years old and consulting for wounds that needed suturing, and we excluded chronic wounds, burns, and hand wounds since they all need special care. During the 1 month, all patients received during ED visit usual verbal instructions concerning the postemergency care (Group A). During the 2 month, all patients received usual verbal instructions and a standardized written advice sheet that detailed postemergency wound care (Group B). We organized telephone follow-up after the suture removal date and asked about dressing changes, appearance of infection signs, and respect of suture removal date. We compared patients;' characteristics in the two groups and performed a multivariable logistic regression using compliance to discharge instructions as our endpoint.

Results: For 2 months, 509 patients consulted for wounds. 119 (23.4%) patients were included in the study and followed. Baseline characteristics of patients did not differ between the two groups. Patients who received the advice sheet (Group B) had a better compliance in postemergency care (91.7% vs. 72.9%; = 0.01). Moreover, there were significantly less dressing changes in Group B than in Group A (5.3 [2.2] vs. 12.9 [7.7]; < 0.01) and suture removal date was more in agreement with recommendations in Group B (83.9% vs. 66.7%; = 0.03). Occurrence of infection was not significantly different between groups (9.7% vs. 13.7%; = 0.37).

Conclusion: For the management of wound care, discharge hospital process including a written advice sheet improves outpatients' compliance and postemergency care.
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http://dx.doi.org/10.4103/2452-2473.301918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864124PMC
December 2020

Anticoagulation Before Hospitalization Is a Potential Protective Factor for COVID-19: Insight From a French Multicenter Cohort Study.

J Am Heart Assoc 2021 04 8;10(8):e018624. Epub 2021 Feb 8.

PARCC INSERM Université de Paris France.

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.
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http://dx.doi.org/10.1161/JAHA.120.018624DOI Listing
April 2021

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality.

Angiogenesis 2021 Jan 15. Epub 2021 Jan 15.

Université de Paris, Institut Cochin, INSERM, 75014 Paris, France, Hematology Department Assistance Publique Hôpitaux de Paris. Centre-Université de Paris (APHP-CUP), Cochin Hospital, 75014, Paris, France.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.

Objectives: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.

Methods: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.

Results: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels.

Conclusion: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
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http://dx.doi.org/10.1007/s10456-020-09762-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809553PMC
January 2021

Dabigatran Level Before Reversal Can Predict Hemostatic Effectiveness of Idarucizumab in a Real-World Setting.

Front Med (Lausanne) 2020 16;7:599626. Epub 2020 Dec 16.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.

Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The aim of the study was to assess the prognostic value of dabigatran plasma level before reversal to test the hemostatic efficacy of idarucizumab. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption. This was an observational multicentric cohort study, which included all French patients who required idarucizumab for dabigatran reversal. Between May 2016 and April 2019, 87 patients from 21 French centers were enrolled. Patients received idarucizumab for overt bleeding ( = 61), urgent procedures ( = 24), or overdose without bleeding ( = 2). Among patients with major bleeding ( = 57), treatment with idarucizumab was considered effective in 44 (77.2%) of them. Patients who did not achieve effective hemostasis after reversal had a significantly higher mean level of plasma dabigatran at baseline (524.5 ± 386 vs. 252.8 ng/mL ± 235, = 0.033). Furthermore, patients who did not achieve effective hemostasis after reversal had less favorable outcomes during follow-up (46.2 vs. 81.8%, = 0.027). ROC curve identified a cutoff of 264 ng/mL for dabigatran level at admission to be predictive of ineffective hemostasis. No plasma dabigatran rebound was observed after reversal in patients with dabigatran plasma level < 264 ng/mL at baseline. This retrospective study shows that dabigatran level before reversal could predict hemostatic effectiveness and dabigatran plasma rebound after idarucizumab injection.
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http://dx.doi.org/10.3389/fmed.2020.599626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772865PMC
December 2020

Predictive Factor for COVID-19 Worsening: Insights for High-Sensitivity Troponin and D-Dimer and Correlation With Right Ventricular Afterload.

Front Med (Lausanne) 2020 12;7:586307. Epub 2020 Nov 12.

Innovative Therapies in Haemostasis, INSERM, Université de Paris, Paris, France.

Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Analyzing the clinical and biological profiles of COVID-19 patients at admission. Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6-96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0-116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76-128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI ( = 0.42, = 0.010) and D-dimer ( = 0.18, = 0.047). Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.
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http://dx.doi.org/10.3389/fmed.2020.586307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689153PMC
November 2020

Merits of expanding the Utstein case definition for out of hospital cardiac arrest.

Resuscitation 2021 01 18;158:88-93. Epub 2020 Nov 18.

Emergency Medical Services Division of Public Health - Seattle & King County, United States; University of Washington School of Medicine, United States. Electronic address:

Background: The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized a system-specific survival correlation between the current Utstein population and other VF populations defined by unwitnessed VF OHCA and VF OHCA after EMS arrival (EMS-witnessed). Expanding performance metrics to this more comprehensive population would make the Utstein definition more representative of the actual community burden and response to VF OHCA.

Methods: We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated > = 100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used Pearson coefficient to assess whether there was a correlation of agency-specific survival outcomes between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA.

Results: A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between the current Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1-2, the Pearson correlation was 0.61.

Conclusion: Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ∼50%, while still achieving a distinguishing metric of system-specific performance.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.041DOI Listing
January 2021

Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells.

Stem Cell Rev Rep 2021 04 17;17(2):639-651. Epub 2020 Nov 17.

Innovative Therapies in Haemostasis, INSERM, Université de Paris, F-75006, Paris, France.

Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34KDR. The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34 and CD19 sub-populations in peripheral blood. After C-TAH implantation, circulating CD34 progenitor cells expressed c-Kit stem marker while specific subsets CD34CD133CD45c-KitKDR were mobilized. KDR was only expressed by CD19 B-lymphocytes and CD14 monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19 in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34 subtypes. In COVID-19, a significant mobilization of CD34c-KitKDR cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34KDR cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19. During COVID-19, a significant mobilization of CD19KDR per million of CD45 cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34c-Kit cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors.Graphical abstract Central illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. Endothelial progenitor cells (EPCs) are involved in cardiovascular diseases, however their phenotype remains elusive. We elucidated here EPCs phenotype by a deep characterization by multidimensional single cell complementary cytometric approaches after Bioprosthetic total artificial heart implantation and during COVID-19. We showed a redistribution of circulating CD34 and CD19 sub-populations in both situations. None of the immature cell population expresses KDR. Mobilized CD34 expressed c-Kit. Imaging flow cytometry demonstrated that CD34KDR cells, after elimination of non-circular events, are all CD19. Our results suggest a new definition of circulating EPCs and emphasize involvement of CD19 cells in cardiovascular disease.
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http://dx.doi.org/10.1007/s12015-020-10062-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670993PMC
April 2021

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

Arterioscler Thromb Vasc Biol 2021 01 5;41(1):415-429. Epub 2020 Nov 5.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, France (N.G., A.B., E.R., S.I., S.L., A. Cras, N.N., J.R., P.G., D.M.S.).

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC) mesenchymal-like phenotype was confirmed by CD90/CD73/CD44 expression and multipotent-like differentiation ability. When VIC were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC-conditioned media and confirmed at the mRNA level in VIC compared with control VIC. Conditioned media from VIC induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC involvement in angiogenesis by a VEGF-A dependent mechanism.

Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
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http://dx.doi.org/10.1161/ATVBAHA.120.314287DOI Listing
January 2021

Endothelial Colony-Forming Cells from Idiopathic Pulmonary Fibrosis Patients Have a High Procoagulant Potential.

Stem Cell Rev Rep 2021 Apr 24;17(2):694-699. Epub 2020 Sep 24.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, AP-HP, Georges Pompidou European Hospital, F-75006 Paris, France, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), 75015, Paris, France.

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive and irreversible lung disease constantly associated with a major vascular remodeling process. Endothelial colony-forming cells (ECFCs) are human vasculogenic cells proposed as a cell therapy product or liquid biopsy in vascular disorders. Since the link between IPF and thrombosis has been largely proposed, the aim of our study was to explore hypercoagulability states in ECFCs from patients with IPF. We performed Thrombin generation assay (TGA) in cord blood (CB)-ECFCs, peripheral blood (PB)-ECFCs and IPF-ECFCs. Endogenous thrombin potential and peak were higher in IPF-ECFCs compared to CB-ECFCs and PB-ECFCs. As thrombin generation in ECFCs was increased, we evaluated anticoagulant proteins expressed on ECFCs membrane and identified thrombomodulin and EPCR. We found a significant decrease of both anticoagulant proteins at membrane using flow cytometry. This study is the first to examine ECFC thrombin generation in IPF. This new finding strongly argues for a role of ECFC in IPF pathophysiology and thrombotic related disorders in IPF. Graphical Abstract.
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http://dx.doi.org/10.1007/s12015-020-10043-4DOI Listing
April 2021

Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation.

Thromb Haemost 2020 Sep 20;120(9):1313-1322. Epub 2020 Jul 20.

Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3-6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values ( = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found ( = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.
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http://dx.doi.org/10.1055/s-0040-1713751DOI Listing
September 2020

Evidence-based guidelines for thromboprophylaxis in patients with lower limb trauma requiring immobilization: an urgent, unmet need.

Eur J Emerg Med 2020 08;27(4):245-246

Emergency Department, Angers university hospital, UMR 1083, UFR santé, Institut Mitovasc, university of Angers, Angers, France.

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http://dx.doi.org/10.1097/MEJ.0000000000000677DOI Listing
August 2020

Curative anticoagulation prevents endothelial lesion in COVID-19 patients.

J Thromb Haemost 2020 09 30;18(9):2391-2399. Epub 2020 Jul 30.

Innovative Therapies in Haemostasis, INSERM, Université de Paris, Paris, France.

Background: Coronavirus disease-2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders.

Objectives: To explore the coagulopathy and endothelial dysfunction in COVID-19 patients.

Methods: The study analyzed clinical and biological profiles of patients with suspected COVID-19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs).

Results: Among 96 consecutive COVID-19-suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS-CoV-2. COVID-19-positive patients were more likely to present with fever (P = .02), cough (P = .03), and pneumonia at computed tomography (CT) scan (P = .002) at admission. Prevalence of D-dimer >500 ng/mL was higher in COVID-19-positive patients (74.2% versus 43.3%; P = .007). No sign of disseminated intravascular coagulation were identified. Adding D-dimers >500 ng/mL to gender and pneumonia at CT scan in receiver operating characteristic curve analysis significantly increased area under the curve for COVID-19 diagnosis. COVID-19-positive patients had significantly more CECs at admission (P = .008) than COVID-19-negative ones. COVID-19-positive patients treated with curative anticoagulant prior to admission had fewer CECs (P = .02) than those without. Interestingly, patients treated with curative anticoagulation and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers had even fewer CECs (P = .007).

Conclusion: Curative anticoagulation could prevent COVID-19-associated coagulopathy and endothelial lesion.
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http://dx.doi.org/10.1111/jth.14968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323356PMC
September 2020

Severity of endothelial dysfunction is associated with the occurrence of hemorrhagic complications in COPD patients treated by extracorporeal CO removal.

Intensive Care Med 2020 10 9;46(10):1950-1952. Epub 2020 Jun 9.

Innovative Therapies in Haemostasis, INSERM UMR-S1140, Paris University, 75006, Paris, France.

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http://dx.doi.org/10.1007/s00134-020-06138-8DOI Listing
October 2020

Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients.

Angiogenesis 2020 11 27;23(4):611-620. Epub 2020 May 27.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006, Paris, France.

Background: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis.

Objectives: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening.

Methods: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission.

Results: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers.

Conclusion: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.
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http://dx.doi.org/10.1007/s10456-020-09730-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250589PMC
November 2020

Temporal trends in the use of targeted temperature management after cardiac arrest and association with outcome: insights from the Paris Sudden Death Expertise Centre.

Crit Care 2019 Dec 3;23(1):391. Epub 2019 Dec 3.

Université de Paris, INSERM, Paris Cardiovascular Research Centre, Paris, France.

Purpose: Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome.

Methods: We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale.

Results: Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 (P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% (P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 (P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome.

Conclusions: We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in "no flow" duration.
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http://dx.doi.org/10.1186/s13054-019-2677-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892202PMC
December 2019

Human Endothelial Colony Forming Cells Express Intracellular CD133 that Modulates their Vasculogenic Properties.

Stem Cell Rev Rep 2019 08;15(4):590-600

Sorbonne Paris Cité, Université Paris Descartes, Paris, France.

Stem cells at the origin of endothelial progenitor cells and in particular endothelial colony forming cells (ECFCs) subtype have been largely supposed to be positive for the CD133 antigen, even though no clear correlation has been established between its expression and function in ECFCs. We postulated that CD133 in ECFCs might be expressed intracellularly, and could participate to vasculogenic properties. ECFCs extracted from cord blood were used either fresh (n = 4) or frozen (n = 4), at culture days <30, to investigate the intracellular presence of CD133 by flow cytometry and confocal analysis. Comparison with HUVEC and HAEC mature endothelial cells was carried out. Then, CD133 was silenced in ECFCs using specific siRNA (siCD133-ECFCs) or scramble siRNA (siCtrl-ECFCs). siCD133-ECFCs (n = 12), siCtrl-ECFCs (n = 12) or PBS (n = 12) were injected in a hind-limb ischemia nude mouse model and vascularization was quantified at day 14 with H&E staining and immunohistochemistry for CD31. Results of flow cytometry and confocal microscopy evidenced the positivity of CD133 in ECFCs after permeabilization compared with not permeabilized ECFCs (p < 0.001) and mature endothelial cells (p < 0.03). In the model of mouse hind-limb ischemia, silencing of CD133 in ECFCs significantly abolished post-ischemic revascularization induced by siCtrl-ECFCs; indeed, a significant reduction in cutaneous blood flows (p = 0.03), capillary density (CD31) (p = 0.01) and myofiber regeneration (p = 0.04) was observed. Also, a significant necrosis (p = 0.02) was observed in mice receiving siCD133-ECFCs compared to those treated with siCtrl-ECFCs. In conclusion, our work describes for the first time the intracellular expression of the stemness marker CD133 in ECFCs. This feature could resume the discrepancies found in the literature concerning CD133 positivity and ontogeny in endothelial progenitors.
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http://dx.doi.org/10.1007/s12015-019-09881-8DOI Listing
August 2019

Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity.

Angiogenesis 2019 05 3;22(2):325-339. Epub 2019 Jan 3.

Hematology Department, AP-HP, European Georges Pompidou Hospital, 20 rue Leblanc, 75015, Paris, France.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties.

Methods And Results: ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis.

Conclusion: To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.
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http://dx.doi.org/10.1007/s10456-018-09659-5DOI Listing
May 2019

Ambulance Density and Outcomes After Out-of-Hospital Cardiac Arrest.

Circulation 2019 03;139(10):1262-1271

Sudden Death Expertise Centre, INSERM U970, Paris, France (R.C., L.L., D.J., W.B., F.B., E.M., X.J., A.C., F.D.).

Background: In out-of-hospital cardiac arrest (OHCA), geographic disparities in outcomes may reflect baseline variations in patients' characteristics but may also result from differences in the number of ambulances providing basic life support (BLS) and advanced life support (ALS). We aimed at assessing the association between allocated ambulance resources and outcomes in OHCA patients in a large urban community.

Methods: From May 2011 to January 2016, we analyzed a prospectively collected Utstein database for all OHCA adults. Cases were geocoded according to 19 neighborhoods and the number of BLS (firefighters performing cardiopulmonary resuscitation and applying automated external defibrillator) and ALS ambulances (medicalized team providing advanced care such as drugs and endotracheal intubation) was collected. We assessed the respective associations of Utstein parameters, socioeconomic characteristics, and ambulance resources of these neighborhoods using a mixed-effect model with successful return of spontaneous circulation as the primary end point and survival at hospital discharge as a secondary end point.

Results: During the study period, 8754 nontraumatic OHCA occurred in the Greater Paris area. Overall return of spontaneous circulation rate was 3675 of 8754 (41.9%) and survival rate at hospital discharge was 788 of 8754 (9%), ranging from 33% to 51.1% and from 4.4% to 14.5% respectively, according to neighborhoods ( P<0.001). Patient and socio-demographic characteristics significantly differed between neighborhoods ( P for trend <0.001). After adjustment, a higher density of ambulances was associated with successful return of spontaneous circulation (respectively adjusted odds-ratio [aOR], 1.31 [1.14-1.51]; P<0.001 for ALS ambulances >1.5 per neighborhood and aOR, 1.21 [1.04-1.41]; P=0.01 for BLS ambulances >4 per neighborhood). Regarding survival at discharge, only the number of ALS ambulances >1.5 per neighborhood was significant (aOR, 1.30 [1.06-1.59] P=0.01).

Conclusions: In this large urban population-based study of out-of-hospital cardiac arrests patients, we observed that allocated resources of emergency medical service are associated with outcome, suggesting that improving healthcare organization may attenuate disparities in prognosis.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035113DOI Listing
March 2019

Early in-hospital management of cardiac arrest from neurological cause: Diagnostic pitfalls and treatment issues.

Resuscitation 2018 11 4;132:147-155. Epub 2018 Aug 4.

Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; INSERM U970, Paris Cardiovascular Research Center, Paris, France; Medical Intensive Care Unit, Cochin Teaching Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.

Purpose: To explore diagnostic pitfalls and treatment issues in out-of-hospital cardiac arrest of neurological cause (OHCA-NC).

Methods: Retrospective analysis of all consecutive patients from the Paris Sudden Death Expertise Centre (France) registry from May 2011 to September 2015 presenting with a sustained return of spontaneous circulation (ROSC) at hospital admission and a final diagnosis of OHCA-NC. Description of the early diagnostic check-up performed to identify the cause of cardiac arrest. Logistic multivariate regression to identify factors associated with immediate coronary angiography (iCAG) in OHCA-NC patients.

Results: Among 3542 patients with ROSC, a final diagnosis of OHCA-NC was established in 247 (7%). The early diagnostic check-up consisted in a total of 207 (84%) immediate cranial CT-scan, 66 (27%) iCAG and 25 (10%) chest CT-scan. The brain CT-scan allowed identifying a neurovascular cause in 116 (47%) patients. An iCAG was performed as the first line exam in 57 (23%) patients, in whom a final diagnosis of neurovascular cause for OHCA-NC was later identified in 41 patients. By multivariate analysis, decision for iCAG was independently associated with ST-segment elevation on post-ROSC electrocardiogram (OR, 5.94; 95%CI, 2.14-18.28; P = 0.0009), whereas an obvious cause of cardiac arrest on scene was negatively associated with iCAG (OR, 0.14; 95%CI, 0.02-0.51; P = 0.01).

Conclusions: OHCA-NC is a rare event that is mainly related to neurovascular causes. The initial ECG pattern may be a confounder regarding triage for early diagnostic check-up. Further studies are required to explore the potential harmfulness associated with decision to perform an iCAG in this population.
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http://dx.doi.org/10.1016/j.resuscitation.2018.08.004DOI Listing
November 2018

Age and benefit of early coronary angiography after out-of-hospital cardiac arrest in patients presenting with shockable rhythm: Insights from the Sudden Death Expertise Center registry.

Resuscitation 2018 07 8;128:126-131. Epub 2018 May 8.

Université Paris-Descartes, Paris, France; Paris-Cardiovascular-Research-Center, INSERM U970, Paris, France; APHP, Hôpital Cochin, Department of Critical Care Unit, Paris, France.

Background: Little is known about the association between provision of post-resuscitation care and prognosis of out-of-hospital cardiac arrest (OHCA) in elderly patients. Previous studies have suggested futility after 65 years of age.

Objectives: We aimed to evaluate the association of early coronary angiogram (CAG) followed if necessary by percutaneous coronary intervention (PCI), with favorable outcome after OHCA among elderly patients, compared to younger patients.

Methods: Using a large French registry, we included all OHCA patients with an initial shockable rhythm, transported to hospital from 2011 to 2015. Favorable outcome was defined as hospital discharge with Cerebral Performance Category (CPC) 1 or 2. and were evaluated by multivariate logistic regression. Subgroup analyses were performed according to age groups: <65, 65-75 and >75 years.

Results: Among 1502 included patients, 31% were older than 65 and 12% older than 75 years. An early CAG was performed in 79%, 88% and 76% of patients below 65, between 65 and 75 and above 75, respectively (P = 0.002). The rate of patients discharged with CPC1 or 2 was 42% below 65, 38% between 65 and 75 and 24% above 75 (P < 0.001). Among the whole population, early CAG (OR = 6.4, 95% CI = 3.9-10.5, P < 0.001) was associated with favorable outcome. In subgroups analysis, CAG was associated with favorable outcome among patients <65 and 65-75. In patients >75, there was a trend towards a favorable outcome (OR2.9, 95CI = 0.9-9.1).

Conclusions: In a large registry of OHCA survivors, the early CAG use was associated with a better prognosis. This benefit was persistent up to 75 years of age, suggesting that age alone should not guide the decision for early invasive strategy.
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http://dx.doi.org/10.1016/j.resuscitation.2018.05.006DOI Listing
July 2018