Publications by authors named "Nathan Mewton"

102 Publications

A lower admission level of interleukin-6 is associated with first-pass effect in ischemic stroke patients.

J Neurointerv Surg 2021 Apr 21. Epub 2021 Apr 21.

Neuroradiology Department, Hospices Civils de Lyon, Lyon, France.

Background: First-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients. We aimed to assess whether admission levels of inflammatory markers are associated with FPE.

Methods: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes AIS patients with large vessel occlusion treated with mechanical thrombectomy following brain MRI. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2, matrix metalloproteinase-9 (MMP-9), soluble P-selectin, and vascular cellular adhesion molecule-1 were measured in admission sera using an ELISA assay. FPE was defined as a complete or near-complete reperfusion (thrombolysis in cerebral infarction scale (TICI) 2c or 3) after the first pass. A multivariate logistic regression analysis was performed to assess independent factors associated with FPE.

Results: A total of 151 patients were included. Among them, 43 (28.5%) patients had FPE. FPE was associated with low admission levels of IL-6, MMP-9, and platelet count, an older age, lack of hypertension, lack of tandem occlusion, a shorter thrombus length, and a reduced procedural time. Following multivariate analysis, a low admission level of IL-6 was associated with FPE (OR 0.66, 95% CI 0.46 to 0.94). Optimal cut-off of IL-6 level for distinguishing FPE from non-FPE was 3.0 pg/mL (sensitivity 92.3%, specificity 42.3%).

Conclusion: A lower admission level of IL-6 is associated with FPE.
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http://dx.doi.org/10.1136/neurintsurg-2021-017334DOI Listing
April 2021

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Eur Heart J 2021 Mar 18. Epub 2021 Mar 18.

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
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http://dx.doi.org/10.1093/eurheartj/ehab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014526PMC
March 2021

Life-threatening arrhythmias in anterior ST-segment elevation myocardial infarction patients treated by percutaneous coronary intervention: adverse impact of morphine.

Eur Heart J Acute Cardiovasc Care 2020 Oct 14. Epub 2020 Oct 14.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, BP 426, 67091 Strasbourg, France.

Aims: Important controversies remain concerning the determinants of life-threatening arrhythmias during ST-segment elevation myocardial infarction (STEMI) and their impact on late adverse events. This study sought to investigate which factors might facilitate ventricular tachycardia (VT) and ventricular fibrillation (VF), in a homogeneous population of anterior STEMI patients defined by abrupt left anterior descending coronary artery (LAD) occlusion and no collateral flow.

Methods And Results: The 967 patients, who entered into the CIRCUS (Does Cyclosporine ImpRove Clinical oUtcome in ST elevation myocardial infarction patients) study, were assessed for further analysis. Acute VT/VF was defined as VT (run of tachycardia >30 s either self-terminated or requiring electrical/pharmacological cardioversion) or VF documented by electrocardiogram or cardiac monitoring, during transportation to the cathlab or initial hospitalization. VT/VF was documented in 136 patients (14.1%). Patients with VT/VF were younger and had shorter time from symptom onset to hospital arrival. Site of LAD occlusion, thrombus burden, area at risk, pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow, and ST-segment resolution were similar to that of patients without VT/VF. There was no impact of VT/VF on left ventricular remodelling or clinical outcomes. By multivariate analysis, the use of morphine (odds ratio 1.71; 95% confidence interval (1.13-2.60); P = 0.012) was the sole independent predictor of VT/VF occurrence.

Conclusions: In STEMI patients with LAD occlusion, our findings support the view that morphine could favour severe ventricular arrhythmias.
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http://dx.doi.org/10.1093/ehjacc/zuaa005DOI Listing
October 2020

Lipid goal achievements after acute myocardial infarction: the gap between real-life and ESC 2019 guidelines.

Eur J Prev Cardiol 2021 Feb 22. Epub 2021 Feb 22.

Service des explorations fonctionnelles cardiovasculaires, Hôpital Louis Pradel, Hospices Civils de Lyon, 28 avenue Doyen Lépine, 69677Bron Cedex, France.

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http://dx.doi.org/10.1093/eurjpc/zwaa160DOI Listing
February 2021

Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol - The COVERT-MI Study.

Cardiology 2021 12;146(2):151-160. Epub 2021 Feb 12.

Centre d'Investigation Clinique, Inserm 1407, CarMeN Unit Inserm 1060, Hôpital Cardiologique Louis Pradel, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Bron, France,

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.
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http://dx.doi.org/10.1159/000512772DOI Listing
February 2021

Kinetics and prognostic value of soluble VCAM-1 in ST-segment elevation myocardial infarction patients.

Immun Inflamm Dis 2021 Feb 8. Epub 2021 Feb 8.

Intensive Cardiological Care Division, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France.

Background: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker of endothelial activation and inflammation. There is still controversy as to whether it can predict clinical outcome after ST-elevation myocardial infarction (STEMI). Our aim was to assess the sVCAM-1 kinetics and to evaluate its prognostic predictive value.

Method: We prospectively enrolled 251 consecutive STEMI patients who underwent coronary revascularization in our university hospital. Blood samples were collected at admission, 4, 24, 48 h and 1 month after admission. sVCAM-1 serum level was assessed using ELISA assay. All patients had cardiac magnetic resonance imaging at 1-month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were recorded over 12 months after STEMI.

Results: sVCAM-1 levels significantly increased from admission up to 1 month and were significantly correlated with IS, LVEF, and LV end-systolic and diastolic volume. (H48 area under curve (AUC) ≥ H48 median) were associated with an increased risk of adverse clinical events during the 12-month follow-up period with a hazard ratio (HR) = 2.6 (95% confidence interval [CI] of ratio = 1.2-5.6, p = .02). The ability of H48 AUC for sVCAM-1 to discriminate between patients with or without the composite endpoint was evaluated using receiver operating characteristics with an AUC at 0.67 (0.57-0.78, p = .004). This ability was significantly superior to H48 AUC creatine kinase (p = .03).

Conclusions: In STEMI patients, high sVCAM-1 levels are associated with a poor clinical outcome. sVCAM-1 is an early postmyocardial infarction biomarker and might be an interesting target for the development of future therapeutic strategies.
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http://dx.doi.org/10.1002/iid3.409DOI Listing
February 2021

Prevalence of low health literacy levels in decompensated heart failure compared with acute myocardial infarction patients.

ESC Heart Fail 2021 Apr 5;8(2):1446-1459. Epub 2021 Feb 5.

Université de Lyon, Université Claude Bernard Lyon 1, Research on Healthcare Performance (RESHAPE), INSERM U1290, Lyon, F-69008, France.

Aims: Health literacy (HL) is a health determinant in cardiovascular diseases as the active participation of patients is essential for optimizing self-management of these conditions. We aimed to estimate the prevalence of low HL level in patients hospitalized for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and explore low HL determinants.

Methods And Results: A prospective cross-sectional study was performed in three cardiology units. HL level was assessed using Brief Health Literacy Screen (BHLS) and categorized as low or adequate. Dimensions of HL were assessed with the Health Literacy Questionnaire (HLQ). Associations with sociodemographic factors, disease history, and comorbidities were explored. A total of 208 patients were included, mean ± SD age was 68.5 ± 14.9 years, and 65.9% were men. Patients with ADHF were significantly older and more often women than AMI patients. Prevalence of low HL was 36% overall, 51% in ADHF patients, and 21% in AMI patients (P < 0.001). After adjustment for sociodemographic factors, patients with lower income (€<10 000 per year, adjusted odds ratio = 10.46 95% confidence interval [2.38; 54.51], P = 0.003) and native language other than French (adjusted odds ratio = 14.36 95% confidence interval [3.76; 66.9], P < 0.002) were more likely to have low HL. ADHF patients presented significantly lower HLQ scores than AMI patients in five out of the nine HLQ dimensions reflecting challenges in access to healthcare.

Conclusions: Prevalence of low HL was higher among ADHF patients than among AMI patients. Low HL ADHF patients needed more support when accessing healthcare services, and these would require more adaptation to respond to low HL patients' needs.
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http://dx.doi.org/10.1002/ehf2.13230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006735PMC
April 2021

It's never too early to beat your low-density lipoprotein cholesterol.

Arch Cardiovasc Dis 2021 Jan 25;114(1):1-3. Epub 2021 Jan 25.

Cardiology Division, Department of Specialties in Medicine, Geneva University Hospitals, 1211 Geneva 14, Switzerland.

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http://dx.doi.org/10.1016/j.acvd.2021.01.001DOI Listing
January 2021

Association of myocardial hemorrhage and persistent microvascular obstruction with circulating inflammatory biomarkers in STEMI patients.

PLoS One 2021 28;16(1):e0245684. Epub 2021 Jan 28.

INSERM U1060, CarMeN Laboratory, Université de Lyon, Groupement Hospitalier Est, Bron, France.

Introduction: Myocardial hemorrhage (IMH) and persistent microvascular obstruction (MVO) are associated with impaired myocardial recovery and adverse clinical outcomes in STEMI patients. However, their relationship with circulating inflammatory biomarkers is unclear in human patients.

Methods And Results: Twenty consecutive patients referred for primary percutaneous coronary intervention of first STEMI were included in a prospective study. Blood sampling was performed at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion for inflammatory biomarker (C reactive protein, fibrinogen, interleukin-6 (IL-6) and neutrophils count) assessment. At seven days, cardiovascular magnetic resonance (CMR) was performed for infarct size, MVO and IMH assessment. Median infarct size was 24.6% Interquartile range (IQR) [12.0-43.5] of LV mass and edema was 13.2% IQR [7.7-36.1] of LV mass. IL-6 reached a peak at H24 (5.6 pg/mL interquartile range (IQR) [2.5-17.5]), CRP at H48 (11.7 mg/L IQR [7.1-69.2]), fibrinogen one week after admission (4.4 g/L IQR [3.8-6.7]) and neutrophils at H12 (9.0 G/L IQR [6.5-12.7]). MVO was present in 11 patients (55% of the study population) and hemorrhage in 7 patients (35%). Patients with IMH had significantly higher IL-6, CRP, fibrinogen, and neutrophils levels compared to patients without IMH. Patients with persistent MVO had significantly higher CRP, fibrinogen and neutrophils level compared to patients without MVO, but identical IL-6 kinetics.

Conclusion: In human patients with acute myocardial infarction, intramyocardial hemorrhage appears to have a stronger relationship with inflammatory biomarker release compared to persistent MVO. Attenuating myocardial hemorrhage may be a novel target in future adjunctive STEMI treatments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245684PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842962PMC
January 2021

Thiamine Deficiency as a Cause for Acute Circulatory Failure: An Overlooked Association in Western Countries.

CJC Open 2020 Nov 19;2(6):716-718. Epub 2020 Jul 19.

Cardiac Intensive Care Unit, Louis Pradel Hospital, Bron, France.

A 42 year-old patient presented with circulatory failure and lactic acidosis. Clinical features, later coupled with biological tests, led to the diagnosis of wet beriberi syndrome and scurvy. Echocardiography showed a pattern of thiamine deficiency with high cardiac output and low vascular resistance. The patient's condition and biological parameters immediately improved after treatment injections of thiamine. Wet BeriBeri is often overlooked in western countries and is a diagnosis that must be considered based on history, and clinical and echocardiographical findings.
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http://dx.doi.org/10.1016/j.cjco.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710995PMC
November 2020

Association of Interleukin-6 Levels and Futile Reperfusion After Mechanical Thrombectomy.

Neurology 2021 02 1;96(5):e752-e757. Epub 2020 Dec 1.

From the Stroke Center (L.M., L.D., E.O., T.-H.C., N.N.), Cardiac Intensive Care Unit (T.B.), Clinical Investigation Center (M.B., C.A., N.M., M.O.), INSERM 1407, Neuroradiology Department (Y.B., O.F.E.), and NeuroBioTec (N.D.), CRB, Hospices Civils de Lyon; and INSERM U1060 (L.M., T.B., A.P., C.C.D.S., E.O., M.O., T.-H.C., N.N.), CarMeN Laboratory, and CREATIS (Y.B.), CNRS UMR 5220, INSERM U1044, University Lyon 1, France.

Objective: To assess whether interleukin-6 (IL-6) level is a marker of futile reperfusion in patients with acute ischemic stroke (AIS) with large vessel occlusion treated with mechanical thrombectomy (MT).

Methods: The Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke (HIBISCUS-STROKE) includes patients with AIS treated with MT after MRI. We performed a sequential assessment of IL-6 (admission, 6 hours, 24 hours, 48 hours and 3 months from admission). Among patients with successful reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3), reperfusion was considered effective if 3-month modified Rankin Scale (mRS) score was 0 to 2 and futile if 3-month mRS score was 3 to 6. Our model was adjusted for the main confounding variables.

Results: One hundred sixty-four patients represent the study population. One hundred thirty-three patients had successful reperfusion (81.1%), while in 46 (34.6%), reperfusion was classified as futile. In single-variable analyses, high IL-6 levels at 6, 24, and 48 hours in combination with a higher age, a prestroke mRS score >2, a history of hypertension or diabetes, lack of current smoking, a higher baseline NIH Stroke Scale score, the absence of associated intravenous thrombolysis, an intracranial internal carotid artery or a tandem occlusion, and an increased infarct growth were associated with futile reperfusion. After multivariable analyses, a high IL-6 level at 24 hours (odds ratio 6.15, 95% confidence interval 1.71-22.10) remained associated with futile reperfusion.

Conclusions: IL-6 is a marker of futile reperfusion in the setting of MT.
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http://dx.doi.org/10.1212/WNL.0000000000011268DOI Listing
February 2021

Predictive value of early cardiac magnetic resonance imaging functional and geometric indexes for adverse left ventricular remodelling in patients with anterior ST-segment elevation myocardial infarction: A report from the CIRCUS study.

Arch Cardiovasc Dis 2020 Nov 5;113(11):710-720. Epub 2020 Nov 5.

Inserm 1407, Clinical Investigation Centre and Heart Failure Department, Cardiovascular Hospital Louis-Pradel, hospices civils de Lyon, université Claude-Bernard Lyon 1, 69677 Bron, France. Electronic address:

Background: Postinfarction adverse left ventricular (LV) remodelling is strongly associated with heart failure events. Conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR).

Aim: To assess the predictive value of the new indexes for 1-year adverse LV remodelling in patients with anterior ST-segment elevated myocardial infarction (STEMI).

Methods: CMR studies were performed in 129 patients with anterior STEMI (58±12 years; 78% men) from the randomized CIRCUS trial (CMR substudy) treated with primary percutaneous coronary intervention and followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). Conicity index, sphericity index, LVGFI, infarct size and microvascular obstruction (MVO) were assessed by CMR performed 5±4 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume of ≥15% by transthoracic echocardiography at 1 year.

Results: Adverse LV remodelling occurred in 27% of patients at 1 year. Infarct size and MVO were significantly predictive of adverse LV remodelling: odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05 (P<0.001) and OR 1.12, 95% CI 1.05-1.22 (P<0.001), respectively. Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR 1.10, 95% CI 1.03-1.16; P=0.001). In multivariable analysis, infarct size remained an independent predictor of adverse LV remodelling at 1 year (OR 1.05, 95% CI 1.02-1.08; P<0.001). LVGFI and infarct size were associated with occurrence of MACE: OR 1.21, 95% CI 1.08-1.37 (P<0.001) and OR 1.02, 95% CI 1.00-1.04 (P=0.018), respectively. Conicity and sphericity indexes were not associated with MACE.

Conclusions: LVGFI was associated with adverse LV remodelling and MACE 1 year after anterior STEMI.
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http://dx.doi.org/10.1016/j.acvd.2020.05.024DOI Listing
November 2020

Imaging Interstitial Fibrosis, Left Ventricular Remodeling, and Function in Stage A and B Heart Failure.

JACC Cardiovasc Imaging 2020 Aug 16. Epub 2020 Aug 16.

Cardiovascular Hospital Louis Pradel, Clinical Investigation Center and Heart Failure Department, INSERM 1407, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France. Electronic address:

Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.
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http://dx.doi.org/10.1016/j.jcmg.2020.05.036DOI Listing
August 2020

Kinetic modelling of myocardial necrosis biomarkers offers an easier, reliable and more acceptable assessment of infarct size.

Sci Rep 2020 08 12;10(1):13597. Epub 2020 Aug 12.

Loire Valley Cardiovascular Collaboration, Université de Tours, EA 4245 T2I & FHU SUPORT, Tours, France.

Infarct size is a major prognostic factor in ST-segment elevation myocardial infarction (STEMI). It is often assessed using repeated blood sampling and the estimation of biomarker area under the concentration versus time curve (AUC) in translational research. We aimed at developing limited sampling strategies (LSS) to accurately estimate biomarker AUC using only a limited number of blood samples in STEMI patients. This retrospective study was carried out on pooled data from five clinical trials of STEMI patients (TIMI blood flow 0/1) studies where repeated blood samples were collected within 72 h after admission to assess creatine kinase (CK), cardiac troponin I (cTnI) and muscle-brain CK (CK-MB). Biomarker kinetics was assessed using previously described biomarker kinetic models. A number of LSS models including combinations of 1 to 3 samples were developed to identify sampling times leading to the best estimation of AUC. Patients were randomly assigned to either learning (2/3) or validation (1/3) subsets. Descriptive and predictive performances of LSS models were compared using learning and validation subsets, respectively. An external validation cohort was used to validate the model and its applicability to different cTnI assays, including high-sensitive (hs) cTnI. 132 patients had full CK and cTnI dataset, 49 patients had CK-MB. For each biomarker, 180 LSS models were tested. Best LSS models were obtained for the following sampling times: T4-16 for CK, T8-T20 for cTnI and T8-T16 for CK-MB for 2-sample LSS; and T4-T16-T24 for CK, T4-T12-T20 for cTnI and T8-T16-T20 for CK-MB for 3-sample LSS. External validation was achieved on 103 anterior STEMI patients (TIMI flow 0/1), and the cTnI model applicability to recommended hs cTnI confirmed. Biomarker kinetics can be assessed with a limited number of samples using kinetic modelling. This opens the way for substantial simplification of future cardioprotection studies, more acceptable for the patients.
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http://dx.doi.org/10.1038/s41598-020-70501-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423884PMC
August 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

Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy.

Front Neurol 2020 9;11:473. Epub 2020 Jun 9.

Stroke Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France.

To assess the relationship between matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and infarct growth and hemorrhagic transformation in acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the era of mechanical thrombectomy (MT) using the kinetics of MMP-9 and sequential magnetic resonance imaging (MRI). HIBISCUS-STROKE is a cohort study including AIS patients with LVO treated with MT following admission MRI. Patients underwent sequential assessment of MMP-9, follow-up CT at day 1, and MRI at day 6. The CT scan at day 1 classified any hemorrhagic transformation according to the European Co-operative Acute Stroke Study-II (ECASS II) classification. Infarct growth was defined as the difference between final Fluid-Attenuated Inversion Recovery volume and baseline diffusion-weighted imaging volume. Conditional logistic regression analyses were adjusted for main confounding variables including reperfusion status. One hundred and forty-eight patients represent the study population. A high MMP-9 level at 6 h from admission (H6) ( = 0.02), a high glucose level ( = 0.01), a high temperature ( = 0.04), and lack of reperfusion ( = 0.02) were associated with infarct growth. A high MMP-9 level at H6 ( = 0.03), a high glucose level ( = 0.03) and a long delay from symptom onset to groin puncture ( = 0.01) were associated with hemorrhagic transformation. In this MT cohort study, MMP-9 level at H6 predicts infarct growth and hemorrhagic transformation.
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http://dx.doi.org/10.3389/fneur.2020.00473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296118PMC
June 2020

Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion.

Stroke 2020 07 17;51(7):2232-2235. Epub 2020 Jun 17.

Stroke Department (L.M., L.D., E.O., T.-H.C., N.N.), Hospices Civils de Lyon, France.

Background And Purpose: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy.

Methods: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0-2) and good (Higashida score, 3-4). A multiple logistic regression model was performed to detect independent markers of good collateral status.

Results: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels (=0.01), high MCP-1 levels (<0.01), a low National Institute of Health Stroke Score (=0.046), a high diastolic blood pressure (=0.049), the absence of tandem occlusion (=0.046), a high Alberta Stroke Program Early CT Score (<0.01) and a low volume on the diffusion-weighted imaging (<0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels (=0.02) and high MCP-1 levels (<0.01) remained associated with good collateral status.

Conclusions: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.
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http://dx.doi.org/10.1161/STROKEAHA.120.029395DOI Listing
July 2020

Myocardial infarction: Economic, health, and social impacts on informal caregivers.

Int J Technol Assess Health Care 2020 Jun 21;36(3):245-251. Epub 2020 Apr 21.

Hospices Civils de Lyon, Pôle de Santé Publique, Lyon, France.

Objectives: The aim of the study was to measure the economic impact of informal care (IC) on caregivers assisting myocardial infarction (MI) survivors in France. Health and social impacts were also described.

Methods: Data from the prospective 2008 Health and Disabilities Households Survey (Enquête Handicap-Santé), carried out among the French general population, were used to obtain information about patients with MI and their informal caregivers. To estimate the approximate monetary value of IC, three methods were used: the proxy good method, opportunity cost method (OCM), and contingent valuation method (CVM). A multivariate analysis was performed to determine the associations of the IC duration and the existence of professional care with the health indicators stated by caregivers.

Results: The analysis included data from 147 caregivers. The mean value of IC ranged from €9,679 per year using the CVM to €11,288 per year using the OCM (p > .05). The mean willingness to pay for an additional hour of IC was €10.9 (SD = 8.3). A total of 46.2 percent of caregivers reported that IC negatively affected theirs physical condition, and 46.3 percent reported that it negatively affected their psychological health. In addition, 40.1 percent declared that caregiving activity made them anxious and 38.8 percent stated they felt alone. Associations were identified between the duration of IC and feeling the need to be replaced, feeling alone and making sacrifices (p < .05).

Conclusions: Informal caregiver burden may be recognized in health technology assessment in order not to underestimate the cost of strategies and to facilitate the comparability of cost-effectiveness outcomes between studies.
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http://dx.doi.org/10.1017/S0266462320000148DOI Listing
June 2020

MRI of Reperfused Acute Myocardial Infarction Edema: ADC Quantification versus T1 and T2 Mapping.

Radiology 2020 Jun 24;295(3):542-549. Epub 2020 Mar 24.

From the Univ Lyon, UJM-Saint-Etienne, INSA, CNRS UMR 5520, INSERM U1206, CREATIS, Saint-Etienne, France (K.M., M.V., W.R., A.C., P.C.); Department of Radiology, Centre Hospitalier Universitaire de Saint Etienne, CREATIS UMR 5020, INSERM U1206, Avenue Albert Raimond, 42000 Saint Etienne Cedex, France (M.V., P.C.); Hôpital Cardiologique Louis Pradel, Centre d'Investigation Clinique, INSERM 1407, Lyon, France (N.M.); and Department of Cardiology, University Hospital Saint Etienne, Université Jean Monnet, Saint Etienne, France (K.I.).

Background After acute myocardial infarction (AMI), reperfusion injury is associated with microvascular lesions and myocardial edema. Purpose To evaluate the performance of apparent diffusion coefficient (ADC) quantification compared with T1 and T2 values in the detection of acute myocardial injury. Materials and Methods In this prospective study conducted from June 2016 to November 2018, participants without a history of heart failure or cardiomyopathy were enrolled after undergoing reperfusion for their first AMI. Quantitative T1 and T2 mapping were performed with a 1.5-T MRI scanner and compared with a fast free-breathing acquisition technique for ADC mapping (approximate duration, 3 minutes; five slices; spin-echo cardiac diffusion acquisition; values, 0 and 200 sec/mm; six diffusion-encoding directions; five repetitions). Quantitative ADC and unenhanced T1 and T2 values were compared in infarct, border, and remote regions by using Welch analysis of variance with Games-Howell post hoc test for pairwise comparisons. Results Thirty-four participants with AMI underwent MRI an average of 5 days ± 1.9 (standard deviation) after reperfusion. Mean ADC was markedly high in the infarcted regions (2.32 × 10 mm/sec; 95% confidence interval [CI]: 2.28, 2.36) and moderately high in the border regions (1.91 ×10 mm/sec; 95% CI: 1.89, 1.94; < .001). In remote regions, mean ADC (1.62 ×10 mm/sec; 95% CI: 1.59, 1.64) was comparable to that measured in vivo in healthy volunteers. Within the same regions of interest, although the measures showed similar trends in infarct and remote regions for T1 (mean, 1332 mec [95% CI: 1296, 1368] vs 1045 msec [95% CI: 1034, 1056]; < .001) and T2 (72 msec [95% CI: 69, 75] vs 50 msec [95% CI: 49, 51]; < .001), the magnitude of the differences among regions was greater when using ADC. Normalized signal differences between infarct and remote regions showed that diffusion-weighted MRI depicted edema 5.1 ( < .001) and 3.5 ( < .001) times greater than did T1 and T2 maps, respectively. Conclusion Multislice cardiac diffusion-weighted images could be acquired in those with acute myocardial injury. Quantitative apparent diffusion coefficient mapping showed greater differences among remote regions and lesions than did T1 or T2 mapping. © RSNA, 2020 See also the editorial by Lloyd and Farris in this issue.
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http://dx.doi.org/10.1148/radiol.2020192186DOI Listing
June 2020

To clip, or not to clip heart failure patients, that is the question.

Eur J Heart Fail 2020 01;22(1):16-19

Hospices Civils de Lyon, Service de Pharmacologie et de Toxicologie. CNRS, UMR5558, Département Biostatistiques et Modélisation pour la Santé et l'Environnement, Equipe Evaluation et Modélisation des Effets des Médicaments, Laboratoire de Biométrie et Biologie Evolutive, Lyon, France.

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http://dx.doi.org/10.1002/ejhf.1612DOI Listing
January 2020

Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients.

Basic Res Cardiol 2019 12 12;115(1). Epub 2019 Dec 12.

INSERM UMR 1060, CarMeN Laboratory, University Claude Bernard Lyon1, IHU OPeRa, Hôpital Louis Pradel, Hospices Civils de Lyon, 69677, Lyon, France.

Despite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit of a single intravenous bolus of cyclosporine in 969 patients with anterior STEMI. Since cyclosporine had no detectable effect on clinical outcomes as well as on any measured variable, we here considered the whole study population as one group. Multivariate analysis was performed to address the respective weight of infarct size and variables in clinical outcomes. Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year. The relative weight of infarct size and variables on the composite endpoint of [death or hospitalization for heart failure] at 1 year was 18% and 82%, respectively. Several variables contribute strongly to the clinical outcomes of STEMI patients suggesting that cardioprotective strategy might not only focus on infarct size reduction.
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http://dx.doi.org/10.1007/s00395-019-0764-8DOI Listing
December 2019

Mechanical circulatory support with the Impella® LP5.0 pump and an intra-aortic balloon pump for cardiogenic shock in acute myocardial infarction: The IMPELLA-STIC randomized study.

Arch Cardiovasc Dis 2020 Apr 15;113(4):237-243. Epub 2019 Nov 15.

Department of Intensive Cardiac Care, Hôpital Louis Pradel, Hospices Civils de Lyon, 59, boulevard Pinel, 69677 Bron, France. Electronic address:

Background: Percutaneous assist devices may be used as a bridge to recovery in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI).

Aim: To test the hypothesis that the Impella® LP5.0 pump (Abiomed Europe GmbH, Aachen, Germany) provides haemodynamic benefits and improves left ventricular ejection fraction (LVEF) in patients with CS-AMI already managed with an intra-aortic balloon pump (IABP).

Methods: This was a prospective randomized study. The primary endpoint was change in cardiac power index (CPI) from baseline to 12hours after implantation, measured with a Swan-Ganz catheter. Secondary endpoints included LVEF at 30 days.

Results: Fifteen patients with CS-AMI were randomized; 12 were available for primary endpoint analysis (IABP group, n=6; Impella LP5.0+IABP group, n=6). Baseline characteristics were similar in both groups. Change in CPI after 12hours was not significantly different between the two groups (IABP group: ΔCPI=0.08±0.08W/m; Impella LP5.0+IABP group: ΔCPI=-0.02±0.25W/m; P=0.4). There was no significant change from baseline CPI in either group over 96hours, and no difference in CPI between groups at each timepoint. In the Impella LP5.0+IABP group, the part of the CPI provided by the native heart decreased from 0.37±0.10 to 0.10±0.20 (P=0.01). LVEF was similar at baseline (29.7%±8.4% and 29.3%±6.7%) and 1 month (40.6%±12.5% and 38.6%±14.4%) in the IABP and Impella LP5.0+IABP groups, respectively. Adverse events, especially major bleeding, were common, and occurred mainly in the Impella LP5.0+IABP group.

Conclusions: In patients with CS-AMI stabilized by initial treatment with inotropes and an IABP, the Impella LP5.0 did not provide additional haemodynamic support or improvement in LVEF at 1 month; its use in this setting might be futile and possibly harmful.
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http://dx.doi.org/10.1016/j.acvd.2019.10.005DOI Listing
April 2020

Regression of Q waves and clinical outcomes following primary PCI in anterior STEMI.

J Electrocardiol 2019 Oct 20. Epub 2019 Oct 20.

Hopital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon, Lyon, France, Centre d'Investigation Clinique de Lyon, Université Claude Bernard Lyon 1, France. Electronic address:

Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after reperfusion with clinical outcomes after anterior STEMI.

Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had regression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.

Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave regression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 ± 2784 IU/l vs. 3814 ± 2595 IU/l vs. 1733 ± 1583 IU/l respectively, p < 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).

Conclusion: In a population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.09.022DOI Listing
October 2019

Economic valuation of informal care provided to people after a myocardial infarction in France.

BMC Health Serv Res 2019 Oct 28;19(1):763. Epub 2019 Oct 28.

Hospices Civils de Lyon, Pôle de Santé Publique, Service d'Evaluation Economique en Santé, 162, avenue Lacassagne - Bâtiment A, 69424, Cedex 03, Lyon, France.

Background: The aim of this study was to estimate the mean cost per caregiver of informal care during the first year after myocardial infarction event in France.

Methods: We used the Handicap-Santé French survey carried out in 2008 to obtain data about MI survivors and their caregivers. After obtaining the total number of informal care hours provided by caregiver during the first year after MI event, we estimated the value of informal care using the proxy good method and the contingent valuation method.

Results: For MI people receiving informal care, an annual mean cost was estimated at €12,404 (SD = 13,012) with the proxy good method and €12,798 (SD = 13,425) with the contingent valuation method per caregiver during the first year after myocardial infarction event.

Conclusions: The present study suggests that informal care should be included more widely in economic evaluations in order not to underestimate the cost of diseases which induce disability.
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http://dx.doi.org/10.1186/s12913-019-4637-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819474PMC
October 2019

Multimodal cardioprotective strategy in cardiac surgery (the ProCCard trial): Study protocol for a multicenter randomized controlled trial.

Trials 2019 Sep 11;20(1):560. Epub 2019 Sep 11.

Service d'Anesthésie-Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon, F-69677, Lyon, France.

Background: Myocardial damage in patients undergoing cardiac surgery increases both morbidity and mortality. Different protective strategies dealing with either preconditioning or postconditioning or assessing a single aspect of cardioprotection have shown conflicting results. We tested the hypothesis that a multimodal approach would improve cardioprotection and limit myocardial damage following cardiac surgery with cardiopulmonary bypass.

Methods: This study is a pragmatic multicenter (six French institutions), prospective, randomized, single-blinded, controlled trial. The randomization is stratified by centers. In the study, 210 patients scheduled for aortic valve surgery with or without coronary artery bypass grafting will be assigned to a control or a treatment group (105 patients in each group). In the control group, patients receive total intravenous anesthesia with propofol and liberal intraoperative blood glucose management (initiation of insulin infusion when blood glucose, measured every 60 min, is greater than 180 mg/dl), as a standard of care. The treatment group receives a bundle of care combining five techniques of cardioprotection: (1) remote ischemic preconditioning applied before aortic cross-clamping; (2) maintenance of anesthesia with sevoflurane; (3) tight intraoperative blood glucose management (initiation of insulin infusion when blood glucose, measured every 30 min, is greater than 140 mg/dl); (4) moderate respiratory acidosis (pH 7.30) at the end of cardiopulmonary bypass; and (5) a gentle reperfusion protocol following aortic unclamping. The primary outcome is myocardial damage measured by postoperative 72-h area under the curve of high-sensitivity cardiac troponin I.

Discussion: The ProCCard study will be the first multicenter randomized controlled trial aiming to assess the role of a bundle of care combining several cardioprotective strategies to reduce myocardial damage in patients undergoing cardiac surgery with cardiopulmonary bypass.

Trial Registration: ClinicalTrials.gov, NCT03230136 . Registered on July 26, 2017. Last updated on April 17, 2019.
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http://dx.doi.org/10.1186/s13063-019-3638-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737694PMC
September 2019

Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years.

Eur J Heart Fail 2019 12 18;21(12):1619-1627. Epub 2019 Nov 18.

Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Service de Biostatistique - Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Villeurbanne, France.

Aims: The MITRA-FR trial showed that among symptomatic patients with severe secondary mitral regurgitation, percutaneous repair did not reduce the risk of death or hospitalization for heart failure at 12 months compared with guideline-directed medical treatment alone. We report the 24-month outcome from this trial.

Methods And Results: At 37 centres, we randomly assigned 304 symptomatic heart failure patients with severe secondary mitral regurgitation (effective regurgitant orifice area >20 mm or regurgitant volume >30 mL), and left ventricular ejection fraction between 15% and 40% to undergo percutaneous valve repair plus medical treatment (intervention group, n = 152) or medical treatment alone (control group, n = 152). The primary efficacy outcome was the composite of all-cause death and unplanned hospitalization for heart failure at 12 months. At 24 months, all-cause death and unplanned hospitalization for heart failure occurred in 63.8% of patients (97/152) in the intervention group and 67.1% (102/152) in the control group [hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.77-1.34]. All-cause mortality occurred in 34.9% of patients (53/152) in the intervention group and 34.2% (52/152) in the control group (HR 1.02, 95% CI 0.70-1.50). Unplanned hospitalization for heart failure occurred in 55.9% of patients (85/152) in the intervention group and 61.8% (94/152) in the control group (HR 0.97, 95% CI 0.72-1.30).

Conclusions: In patients with severe secondary mitral regurgitation, percutaneous repair added to medical treatment did not significantly reduce the risk of death or hospitalization for heart failure at 2 years compared with medical treatment alone.
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http://dx.doi.org/10.1002/ejhf.1616DOI Listing
December 2019

Impact of Collateral Status on Neuroprotective Effect of Cyclosporine A in Acute Ischemic Stroke.

Curr Neurovasc Res 2019 ;16(2):173-177

Department of Neuroradiology, University Lyon 1, CREATIS, CNRS-UMR5220 INSERM-U1044, Lyon, France.

Background: Neuroprotection for acute ischemic stroke remains an elusive goal. Intracranial collaterals may favor neuroprotective drugs delivery at the acute stage of ischemic stroke. A recent phase 2 study showed that cyclosporine A (CsA) reduced ischemic damage in patients with a proximal occlusion who experienced effective recanalization. Collateral flow may improve this benefit.

Materials & Methods: Collateral supply was assessed using dynamic susceptibility contrast MRI in 47 patients among the 110 patients from the original study and were graded in two groups: good collaterals and poor collaterals. Patients with good collaterals had significantly smaller initial infarct in both CsA group (p = 0.003) and controls (p = 0.016). Similarly, the final lesion volume was significantly lower in patients with good collaterals in both groups.

Results: In patients with either good or poor collaterals CsA showed no additional benefit on ischemic lesion progression and final infarct size at day 30.

Conclusion: We failed to demonstrate any significant additional benefit of CsA in patients with good collateral circulation.
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http://dx.doi.org/10.2174/1567202616666190618094014DOI Listing
July 2020