[Show abstract][Hide abstract] ABSTRACT: Background Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. Methods In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. Results A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. Conclusions In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774 ; EudraCT number, 2009-013713-99 .).
New England Journal of Medicine 08/2015; DOI:10.1056/NEJMoa1505489 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionThere are little data about patients with cardiogenic shock (CS) who survive the early phase of acute myocardial infarction (AMI). The aim of this study was to assess long-term (5-year) mortality among early survivors of AMI, according to the presence of CS at the acute stage.Methods
We analyzed 5-year follow-up data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 registry, a nationwide French survey including consecutive patients admitted for ST or non-ST-elevation AMI at the end of 2005 in 223 institutions.ResultsOf 3670 patients enrolled, shock occurred in 224 (6.1%), and 3411 survived beyond 30 days or hospital discharge, including 99 (2.9%) with shock. Early survivors with CS had a more severe clinical profile, more frequent concomitant in-hospital complications, and were less often managed invasively than those without CS.Five-year survival was 59% in patients with, versus 76% in those without shock (adjusted hazard ratio (HR)¿=¿1.72 [1.24-2.38], P¿=¿0.001). The excess of death associated with CS, however, was observed only during the first year (one-year survival: 77% vs 93%, adjusted HR: 2.87 [1.85 to 4.46] P <0.001), while survival from one to 5 years was similar (76% vs 82%, adjusted HR: 1.06 [0.64 to 1.74]). Propensity score-matched analyses yielded similar results.Conclusions
In patients surviving the early phase of AMI, CS at the initial stage carries an increased risk of death up to one year after the acute event. Beyond one year, however, mortality is similar to that of patients without shock.ClinicalTrials.gov number, NCT00673036, Registered May 5, 2008.
[Show abstract][Hide abstract] ABSTRACT: Aims:
Fondaparinux is an alternative to low molecular weight heparin (LMWH) for non-ST-elevation myocardial infarction (NSTEMI) with levels of recommendation that differ according to guidelines. The aim of this study was to assess outcomes in real world practice in NSTEMI patients participating in the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 according to the use of fondaparinux, in comparison with patients receiving enoxaparin.
Methods and results:
FAST-MI 2010 is a nationwide French registry that included 4,169 patients with acute myocardial infarction at the end of 2010 in 213 centres (76% of active centres in France); 1,734 had NSTEMI, with 240 receiving fondaparinux and 1,027 enoxaparin. Patients receiving enoxaparin vs. fondaparinux had essentially characteristics with a similar GRACE (Global Registry of Acute Coronary Events) score. Invasive strategy was used in 69% in both groups. In-hospital bleeding was similar with both anticoagulant strategies and 1-year survival was 94.6% and 91.7%, respectively. Using fully adjusted Cox multivariate analysis, the use of fondaparinux was not associated with a reduced risk of death (hazard ratio: 1.35; 95% confidence interval: 0.70-2.51). After propensity score matching (207 patients per group), 1-year survival was similar with both strategies. There was, however, an interaction between fondaparinux and unfractionated heparin, with higher survival in fondaparinux-treated patients who received UFH, compared with those who did not.
In this French cohort of NSTEMI patients, predominantly managed invasively, there was no evidence that fondaparinux was superior to enoxaparin as regards bleeding events or 1-year mortality (FAST-MI 2010; NCT01237418).
European Heart Journal: Acute Cardiovascular Care 07/2014; 4(3). DOI:10.1177/2048872614544857
[Show abstract][Hide abstract] ABSTRACT: L’évolution rapide des méthodes de dosage des troponines cardiaques (cTn) vers une meilleure sensibilité analytique (cTn de haute sensibilité ou cTn HS) s’accompagne de nombreuses données de la littérature, mais encore incomplètes. En l’absence de standardisation des cTn et de données consensuelles sur l’utilisation et l’interprétation des résultats, les auteurs de cette revue proposent, à partir d’une revue de la littérature, et de façon multidisciplinaire, des éléments de réponses aux questions fréquemment posées. En conclusion, le bon usage des cTn HS repose sur la connaissance : 1) des caractéristiques propres de la méthode utilisée, en particulier de la précision obtenue au 99e percentile d’une population de référence ; 2) des facteurs de variation de la valeur du 99e percentile ; 3) de la forte individualité des dosages de cTn HS, pour lesquels la notion de cinétique individuelle est plus informative que la simple référence à des valeurs usuelles. La significativité des variations entre deux dosages n’est pas encore documentée pour toutes les méthodes HS. La collaboration entre cliniciens et biologistes est nécessaire à une meilleure utilisation des troponines au quotidien.
The recent evolution of cardiac troponin assays (cTn) for acquisition of a better analytical sensitivity (high-sensitivity cTn, or cTn HS) is widely described in the literature; however, actual data remain incomplete. Considering the absence of cTn assays standardisation and of consensual data for using and interpreting cTn results, the authors propose multidisciplinary responses to frequently asked questions. Proper use of cTn HS relies upon knowledge of 1) the assay characteristics, and mainly the observed precision at the 99th percentile value; 2) the variation factors of the 99th percentile value; and 3) the high individuality of cTn HS tests, for which the notion of kinetics is more informative than the single reference to ‘normal’ values. Significant variation between 2 measurements, is not already documented for every HS assay. A strong partnership between clinicians and biologists is needed for a better understanding and use of cTn HS in routine.
Annales Francaises de Medecine d'Urgence 07/2014; 4(4):221-241. DOI:10.1007/s13341-014-0423-5
[Show abstract][Hide abstract] ABSTRACT: Aims:
The relationship of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) with myocardial biomarkers and markers of inflammation in acute viral myocarditis is not clearly defined. We assessed the relationship of LGE with myocardial and inflammatory biomarkers measured during the acute phase of myocarditis and their predictive value on clinical outcome.
Patients with first clinical episode of acute viral myocarditis and complete CMR study, including cine and LGE images, were included. The peak values of troponin I, creatine kinase, C-reactive protein value at admission and LGE extent were reported for each case. A 29-month clinical follow-up was performed, and cardiac symptoms and adverse cardiac events (all-cause death, heart transplant, hospitalization for heart failure) were reported.
Forty-one patients (39 ± 15 years and 78% men) were included. Median LGE extent was 13% [interquartile range (IQR) (9%, 19%)] of left-ventricular mass and mean left-ventricular ejection fraction was 56 ± 11%. There was a significant correlation between peak troponin I and LGE extent (r = 0.51, P < 0.001), and between peak creatine kinase and LGE extent (r = 0.66, P < 0.001). There was no correlation between C-reactive protein at admission and LGE extent (r = 0.27, P = 0.09). At follow-up, eight (20%) patients had an adverse clinical event. LGE extent was significantly associated with a worse New York Heart Association status at follow-up [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.07, 1.37, P = 0.002]. After adjustment for left-ventricular ejection fraction, age and clinical presentation category, LGE extent remained an independent predictor of cardiovascular events (hazard ratio 1.42; 95% CI 1.05, 1.95, P = 0.027).
LGE extent on CMR studies is significantly correlated to biomarkers of myocardial injury in patients with acute viral myocarditis, and is a significant independent predictor of adverse cardiovascular outcome.
Journal of Cardiovascular Medicine 06/2014; Publish Ahead of Print(10). DOI:10.2459/JCM.0000000000000024 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims: To assess fractional flow reserve (FFR) variability in case of arterial hypotension in the clinical setting. FFR measurement is supposed to be independent of haemodynamics; there is, however, a strong relationship between trans-stenotic pressure variation and coronary flow. Non-clinical models suggest an inverse relationship between arterial pressure and FFR, but no clinical data have as yet confirmed this hypothesis. Methods and results: In case of arterial hypotension (mean arterial pressure [Pa] ≤80 mmHg) during routine clinical FFR measurement (FFR1), a second measurement (FFR2) was performed after pressure normalisation by 0.5 mg IV phenylephrine. Fourteen intermediate chronic stenoses (%DS 58±21%, FFR1=0.81±11) in 12 male patients showed 70±10 mmHg Pa at the time of measurement. After phenylephrine, Pa increased to 101±14 mmHg and FFR2 decreased to 0.75±12 (p<0.001) without heart rate variation. After Pa elevation, 40% of cases with FFR1 >0.80 changed to FFR2 ≤0.80. Conclusions: In the present study, in case of arterial hypotension, FFR decreased with rising pressure. Whether repeated FFR measurement after haemodynamic normalisation is of clinical benefit remains at this point speculative and should be validated in a larger data set.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2014; 11(4). DOI:10.4244/EIJV11I4A82 · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined.
In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR.
This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients.
European Heart Journal 02/2014; 35(25). DOI:10.1093/eurheartj/ehu054 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After acute myocardial infarction, the presence of no-reflow (or microvascular obstruction: MVO) has been associated with adverse left ventricular (LV) remodeling and worse clinical outcome. This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infarction (STEMI) patients. Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to ischemic postconditioning (PC) (n = 25) or control (n = 25) groups. Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the onset of reperfusion. Early (3 min post-contrast) and late (10 min post-contrast) MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after reperfusion. PC was associated with smaller early and late MVO size (3.9 ± 4.8 in PC versus 7.8 ± 6.6 % of LV in controls for early MVO, P = 0.02; and 1.8 ± 3.1 in PC versus 4.1 ± 3.9 % of LV in controls for late MVO; P = 0.01). This significant reduction was persistent after adjustment for thrombus aspiration, which neither had any significant effect on infarct size, nor on early or late MVO (P = NS for all). Attenuation of MVO was associated to infarct size reduction. Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty.
Archiv für Kreislaufforschung 11/2013; 108(6):383. DOI:10.1007/s00395-013-0383-8 · 5.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deformation imaging is undergoing continuous development with the emergence of new technologies allowing the evaluation of the different components of strain simultaneously in three dimensions. Assessment of all global strain parameters in 2D and 3D modes and comparison with LVEF have been the focus of our study.
Out of 166 patients, 147 were evaluated with the use of both 2D and 3D speckle-tracking echocardiography (STE). Global strain parameters including longitudinal (GLS), circumferential (GCS), radial (GRS) and area strain (AS), as well as left ventricular volumes and ejection fraction were examined. Analysis of strain with 3D STE was faster than with 2D STE (7 ± 2 vs. 24 ± 4 min, P < 0.05). GLS values were similar between 2D and 3D modes (-14 ± 4 vs. -13 ± 3, NS), while slight differences were observed for GCS (-24 ± 7 vs. -27 ± 7, P < 0.05) and GRS (27 ± 9 vs. 24 ± 9, P < 0.05). All 2D and 3D strain parameters showed good accuracy in the identification of 2D-LVEF <55% with AS demonstrating superiority over GCS and GRS but not GLS.
Three-dimensional STE allows accurate and faster analysis of deformation when compared with 2D STE and might represent a viable alternative in the evaluation of global LV function.
[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that the decrease in ventricular septal rupture (VSR) incidence after acute myocardial infarction is related to the improvement of reperfusion strategies. Our main objective was to explore the influence of therapeutic management changes on post-infarct VSR patient outcomes in a single reference center over a period of 30 years. We analyzed therapeutic management strategies and mortality rates in 228 patients with VSR after acute myocardial infarction admitted from 1981 to 2010. Patients were classified in 3 successive decades. There were no significant differences in clinical characteristics of patients with VSR at admission among those decades. Overall, surgery was performed in 159 patients (71.9%), primary transcatheter VSR closure was attempted in 5 patients (2.2%), and 64 patients (27.6%) were managed medically. Independent predictors of in-hospital mortality were VSR surgical repair (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.1 to 0.7, p = 0.008), cardiogenic shock (OR 6.06, 95% CI 2.8 to 13.1, p <0.0001), and Killip class on admission (OR 1.75, 95% CI 1.1 to 9.9, p = 0.02). We found a significant 1-year mortality reduction between the first and second decades (hazard ratio 0.48, 95% CI 0.28 to 0.80; p = 0.005), with no significant change in the last decade (p = 0.2). This change was related to a systematic referral to surgical repair and shorter delays to VSR surgery (5.2 ± 6.3 vs 1.9 ± 3.2 days from first to second decade; p = 0.012). In conclusion, surgical repair remains the only significant efficient therapy to reduce mortality in patients with VSR (p <10(-3)). In-hospital prognosis remains disappointing. This contrasts with the favorable long-term outcome of patients who survive the perioperative period and are discharged from hospital.
The American journal of cardiology 07/2013; 112(9). DOI:10.1016/j.amjcard.2013.06.009 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Une méthode fiable et rapide d’exclusion de l’infarctus du myocarde (IDM) représente un objectif médical crucial à atteindre. Une des pistes de la recherche actuelle est d’associer des marqueurs indépendants de la physiopathologie ischémique pour améliorer le diagnostic d’IDM.
Matériel et méthodes
Notre étude, observationnelle, rétrospective et monocentrique, a été réalisée sur une population de patients se présentant au service d’accueil des urgences du centre hospitalier Lyon-Sud pour une douleur thoracique apparue dans les six heures précédentes. Quatre-vingt-trois patients ont été inclus d’âge moyen de 64 ans dont neuf cas d’infarctus non ST+. Son objectif principal a été de déterminer la performance statistique de la copeptine dans l’exclusion des syndromes coronariens sans élévation du segment ST (SCA NST+). L’objectif secondaire a été d’estimer le gain de temps potentiel d’un schéma décisionnel utilisant le couple copeptine-première troponine par rapport au schéma classique double dosage de la troponine dans l’exclusion de l’IDM.
Notre évaluation d’une stratégie double, associant copeptine et le premier dosage de troponine avec un cut-off de 9 pmol/l, retrouve un rapport de vraisemblance négatif proche de 0,0 (0,01–1,92), une sensibilité à 1,0 (IC 95 %: 0,66–1), une valeur prédictive négative à 1,0 (IC 95 %: 0,88–1) et un taux d’erreurs semblant être inférieur à 10 %. Le gain de temps potentiel en utilisant une stratégie double est de 310 minutes, soit un peu plus de cinq heures.
L’association de la copeptine améliore significativement la valeur diagnostique de la troponine pour l’exclusion des SCA NST+ aux urgences, tout en permettant au clinicien de réduire les délais de prise en charge.
Annales Francaises de Medecine d'Urgence 05/2013; 3(3). DOI:10.1007/s13341-013-0303-4
[Show abstract][Hide abstract] ABSTRACT: Purpose: Atherosclerotic plaques progress in a highly individual manner. Plaque eccentricity has been associated with a rupture-prone phenotype and adverse coronary events in humans. Endothelial shear stress (ESS) critically determines plaque growth and low ESS leads to high-risk lesions. However, the factors responsible for rapid disease progression with increasing plaque eccentricity have not been studied. We investigated in vivo the effect of local hemodynamic and plaque characteristics on progressive luminal narrowing with increasing plaque eccentricity in humans.
Methods: Three-dimensional coronary artery reconstruction using angiographic and intravascular ultrasound data was performed in 374 patients at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Trial. A total of 874 coronary arteries were divided into consecutive 3-mm segments. We identified 408 BL discrete luminal narrowings with a throat in the middle surrounded by gradual narrowing proximal and distal to the throat. Local BL ESS was assessed by computational fluid dynamics. The eccentricity index (EI) at BL and FU was computed as the ratio of max to min plaque thickness at the throat. Mixed-effects logistic regression was used to investigate the effect of BL variables on the combined endpoint of substantial worsening of luminal narrowing (decrease in lumen area >1.8 mm2 or >20%) with an increase in plaque EI.
Results: Lumen worsening with an increase in plaque EI was evident in 73 luminal narrowings (18%). Independent predictors of worsening lumen narrowing with plaque EI increase were low BL ESS (<1 Pa) distal to the throat (odds ratio [OR] =2.2 [95% CI: 1.3-3.7]; p=0.003) and large BL plaque burden (>51%) at the throat (OR=1.7 [95% CI: 1.0-2.8]; p=0.051). The incidence of worsening lumen narrowing with increasing plaque eccentricity was 30% in the presence of both predictors versus 15% in luminal narrowings without this combination of characteristics (OR=2.4 [95% CI: 1.4-4.3]; p=0.002).
Conclusions: Low local ESS independently predicts areas with rapidly progressive luminal narrowing and increasing plaque eccentricity. Coronary regions manifesting an abrupt anatomic change, i.e., at highest risk to cause an adverse event, can be identified early by assessment of ESS and plaque burden.