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During myocardial infarction (MI), reperfusion therapy leads to side effects called ischemia-reperfusion (IR) injury for which no treatment exists. While most studies have targeted the intrinsic apoptotic pathway to prevent IR injury with no successful clinical translation, we have developed a cardioprotective tool, the anti-apoptotic Tat-DAXXp (TD) peptide, targeting the FAS-dependent extrinsic pathway and recently evidenced as a potent therapeutic molecule. The aim of the present study was to evaluate TD long-term cardioprotective effects in a mouse model of reperfused infarction. TD peptide was evaluated in a mouse model of myocardial infarction (40 minutes ischemia) followed by reperfusion and 6 months follow-up. TD peptide (1 mg/kg) was administered in mice subjected to MI (TD; n = 21), 5 min prior to reperfusion. Cardiac injury in the study cohort was assessed by the quantification of cardiac Troponin I levels at 24 h post-MI and each month of the period. Pre-clinical evaluation was performed by the mean of echocardiographic follow-up using both conventional and strain parameters. A histological analysis was performed at the end of the protocol for the quantification of fibrosis extend. Plasma cTnI concentration evaluated 24 h post-MI was 70%-decreased in TD (n = 16) versus Ctrl (n = 20) mice (p***). Strain echocardiography highlighted a 24%-increase (p****) in the ejection fraction mean value in TD-treated (n = 12) versus Ctrl mice (n = 17) during the 6-month period. Improved cardiac performance was associated to a 54%-decrease (p**) in left ventricular fibrosis at 6 months in TD (n = 16) versus Ctrl (n = 20). Targeting the extrinsic pathway with the TD peptide at the onset of reperfusion provided long-term cardioprotection in a mouse model of reperfused infarction by improving post-MI cardiac performance and preventing cardiac remodeling. [ABSTRACT FROM AUTHOR]

Ischemic preconditioning and postconditioning are two effective therapeutic strategies for reducing infarct size in animal models and humans. The aim of our study was to compare the early regulated genes of preconditioning and postconditioning using a transcriptomic approach. Methods: C57Bl6, Zac1+/– KO (n=7) and WT littermates (n=4) mice underwent an IR (40 min. ischemia/60 min.reperfusion) protocol. C57Bl6 mice were randomly assigned to different groups: IR (n=22); postconditioning (PostC, n=21): a protocol of 3 cycles of 1-minute reperfusion and 1-minute reocclusion was applied at the onset of reperfusion; preconditioning (PreC, n=15; same algorithm but applied before ischemia. At the end of surgery, left ventricles were assigned to RNA extraction or infarct size assessment. Homemade mouse oligo microarrays were used for gene expression profiling (Montpellier GenomiX Facilities). Determination of area at risk (AR) and infarct size was assessed by TTC staining and planimetry. Results: Our study revealed that despite a similar cardioprotection offered by PreC and PostC on infarct size, PostC regulates a larger number of genes compared to PreC (242 versus 40). Only 8 genes were jointly regulated by PreC and PostC and considered as putative cardioprotective key regulators. Among these candidates, Zac1 was down regulated at the transcriptional levels upon PreC and PostC. Moreover, infarct size/AR was 29%-decreased in Zac1 +/– KO mice subjected to a surgical protocol of myocardial IR. Conclusion: Using pangenomic microarrays, we identified and compared the gene profiles of preconditioning and postconditioning versus IR in the mouse left ventricle in vivo. Among the genes jointly downregulated by preconditioning and postconditioning, Zac1 was identified as a putative cardioprotective key regulator. Indeed downregulation at the transcriptional and protein levels of Zac1 leads to cardioprotection against IR. [Copyright &y& Elsevier]

Cardiac disease occurs in more than 50% of patients with idiopathic hypereosinophilic syndrome; it is the major cause of morbidity and mortality in patients with this syndrome. The overall mortality is high if untreated. We aim to rapport recent experience in these cardiac diseases, especiall echographic features and the contribution of multimodalities imaging. This retrospective, descriptive and multicenter study reports the findings of patients in cardiac centers of Marseille, Montpellier and Rennes between September 2008 and March 2014. Echographic, MRI cardiac, coronarographic, PET CT, biology and histologic findings are reported. Seven patients have been reported. Echocardiography is the reference diagnostic method. Classical findings are progressive endomyocardial thickening, apical obliteration of one or both ventricles by echogenic material suggestive of fibrosis or thrombus formation, posterior mitral leaflet involvement and papillary dysfunction resulting in severe mitral regurgitation. These features are involved in embolic events or heart failure. MRI helps refine the diagnosis. The characteristic irreversible stage shows a circumferential thickened fibrotic sub endocardium with wall thrombi. The CT identifies non ischemic thrombus excluding coronary artery disease by coronary imaging. Coronary angiography may reveal fibrosis by the smoothed appearance of the ventricular walls and apical filling. PET CT shows general signs of myocarditis, such as myocyte necrosis, in the first stage of the disease. Symptomatic treatment can lead to cardiac surgery (mitral valve replacement, resection of endomyocardial fibrosis). Each imaging technique plays a role in each of the three stages of the disease and the typical features of myocarditis, thrombus or fibrosis must be identified. Only seven cases of this rare disease have been identified in three french cardiac centers since 2008; this too small sample does not allow us to draw statistical conclusions. Abstract 0009 - Figure: endomyocardial thickening and mitral involvement [ABSTRACT FROM AUTHOR]

Purpose Acute pericarditis is rather frequent. Annual incidence is estimated to 27.7 new cases per 100,000 inhabitants in Europe. About 5% of all non-ischemic chest pains admitted at emergencies could be pericarditis. Most of the patients are young patients, with a significant cost to society, particularly as regards hospitalizations. Indeed, pericarditis represents 1% of all hospitalizations in department of cardiology. It could be very interesting if clinical presentation and especially heart rate could help predict duration of hospitalizations. Methods Between March 2007 and February 2010, we conducted a retrospective study concerning all patients admitted in our center for acute pericarditis. Diagnosis criteria included 2 among the 4 following: typical chest pain, friction rub, pericardial effusion on echocardiography, or typical ECG findings. We evaluated hospital events (heart failure, acute pains, death) and biology during hospitalization (CRP on admission, on days 1, 2, 3, and especially peak). At one month, clinical events were recorded through phone calls when not noticed in clinical settings. Results We included 73 patients. Mean age was 41.0 y (CI 95% 37.2-44.8) and mean hospitalization duration was 3.5 d (2.5-4.5). Heart rate on admission was 88 bpm (83.6-92.4) and 71.8 bpm (68.9-74.7) on discharge. CRP peak was strongly correlated with heart rate (r=0.54; p<0.0001) and with hospitalization duration (r=0.8; p=0.007). Finally, we found a positive correlation between heart rate on admission and duration of hospitalizations (r=0,226; p<0.06). Fever was scarcely observed (21%), and was not correlated with heart rate and with CRP. Conclusion In acute pericarditis, cardiac frequency at admission is correlated with hospitalization duration, and could be a new prognostic marker. This point deserves to be explored, in order to reduce hospitalization duration. [ABSTRACT FROM AUTHOR]

Purpose In the prospective KaRen registry of heart failure with preserved ejection fraction (HFPEF), changes in clinical and biological parameters and medications were assessed between acute presentation and out-patient follow-up in stable state. Methods The KaRen study included patients presenting with acute heart failure (HF) according to inclusion criteria: Framingham criteria for HF, left ventricular ejection fraction > or=45% and brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients returned as out-patients for repeat assessment. Changes in clinical and biological parameters and medications between inclusion and follow-up were assessed with Students t-test and Chi-square tests Results 577 patients were recruited and 458 returned for the 4-8 weeks visit. 56% were women. The median [25-75pctl] age was 79 [72-84] years. Medical history included 78% hypertension, 58% atrial arrhythmia, 26% type II diabetes and 27% serum creatinin >100 micromol/l. The table provides inclusion and follow-up data Conclusions Patients presenting with HFPEF are elderly and a majority are women, with a high rate of hypertension and atrial arrhythmias. Blood pressure is incompletely controlled. At follow-up, blood pressure and NT-proBNP were reduced, but patients remain symptomatic. Still, efforts are needed to improve symptoms in HFPEF. [ABSTRACT FROM AUTHOR]

Introduction Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit "mechanical inflammation". Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. Methods Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted in our center for acute pericarditis. Diagnosis criteria included 2 among the following: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical ECG findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. We evaluated also recurrences and clinical events during hospitalization and at one month. Results We included 73 patients. Median age was 38.0 y (CI 25-75% 28.0-51.0) and median hospitalization duration was 2.0 d (1.5-3.0). 27% of the patients presented pericardial effusion. Heart rate on admission was 88.0 bpm (CI 25-75%: 76.0-100.0) and on discharge 72.0 (65.0-80.0)). Heart rate on admission was significantly correlated with CRP on admission (r=0.34, n=69; p=0.004), CRP peak (r=0.54; n=61; p<0.0001), CRP on discharge (r=0.32; p=0.021) and temperature on admission (r=0.40; n=39; p=0.01). Multivariate analysis showed that HR on admission is associated with an elevated CRP peak, independently of temperature on admission. Fever was scarcely observed (19.5%), and was neither correlated to HR nor CRP, after multivariate analysis. Conclusion In acute pericarditis, HR on admission is independently correlated with CRP levels. These observations could suggest a link between HR and pericardial inflammation. [ABSTRACT FROM AUTHOR]

Background: Surgery decision in severe mitral regurgitation (MR) depends on left ventricular ejection fraction (LVEF). However better markers are needed to detect early LV dysfunction. Aim: We sought to determine the ability of 2D strain assessed by speckle tracking imaging (STI) to detect subclinical LV dysfunction in severe chronic MR. Methods: We studied 11 patients (8 men, 69±10 years) who had severe organic MR with a LVEF ≥ 55%, and 10 healthy controls (HC). STI was performed to measure longitudinal strain (LS) in 4 and 2 chambers views, in apical long axis view, and to assess global longitudinal strain (GLS). Results: The etiology of MR was degenerative in 10 patients and congenital in 1 patient. MR was severe in all patients (EROA = 66±23 mm2). Comparing HC vs patients, left atrial area was significantly lower (16,6±2 cm2 vs 35±10 cm2 ; p<0,001). There was no difference in LVEF (65,6±6% vs 63,8±3,6% ; p=ns), in end-diastolic volumes (64,5±19 ml/m2 vs 61,5±17 ml/m2 ; p=ns), or in GLS (-20±1,1% vs -21±3,6% ; p=ns). In the patient group, we could distinguish one group with increased GLS (n=7, GLS = -23,5±1,3% ; p<0,01 vs HC), and one with a trend for a lowered GLS (n=4, GLS = -16,6 ±0,5%; p=0,125), but this was probably due to a lack of statistical power (n=4). 3 patients in the second group were in atrial fibrillation showing the impact of MR on left cavities. Inter-observer variability was good (r=0,89). LS was significantly lower in septoapical segment in HC vs patients (-21,6 ±3,5% vs -28,6±4,8% ; p<0,0001), as well as in anteroseptobasal (-16±3,4% vs -20,9±4,5% ; p<0,01) and anteroseptomedian (-18,7±2,8% vs -24,9±5,3% ; p<0,01) segments. Conclusion: In patients with chronic organic MR and LVEF ≥ 55%, two populations may be highlighted by 2D-strain: one with significantly increased GLS and one with a trend for a lowered GLS. More studies are required to evaluate causes and clinical consequences. [Copyright &y& Elsevier]

Background: Right ventricular (RV) function has major prognostic implications for pulmonary arterial hypertension (PAH). RV function assessment by echocardiography is challenging in PAH patients. New techniques such as two-dimensional strain (2DS) and three dimension (3D) echocardiography may allow assessment of RV function. Objective: We sought to determine among echocardiographic techniques – those widely used, 2DS and 3D – which one was the best correlated to magnetic resonance imaging (MRI) measurements. Methods: Fourteen patients with PAH (mean age 58 +/- 17 yr, 7 women) were evaluated. RV fractional area change (RVFAC), Tei index, peak systolic velocity (S), Tricuspid Annular Plane Systolic Excursion (TAPSE) were measured. Global and segmental RV longitudinal deformations were recorded by 2DS echocardiography from 4 apical-chamber views using 6 segments RV model. Echocardiographic system designed for 3D was Tomtec. Results: TAPSE, peak S and RVFAC were lower in PAH patients than control and correlated to MRI (p<0.005). Global and free wall strain measured by 2DS and ejection fraction VD (FEVD) by MRI (r=0.73; p< 0.005) were inversely correlated. The 3D volume and 3D FEVD were strongly correlated to corresponding measurements obtained by MRI (volume: r=0.88; p<0.005) (FE: r=0.85; p<0.005). Conclusion: Both 2DS and 3D echocardiography techniques are strongly correlated to MRI. Simple and reliable 2DS could be preferred to 3D. [Copyright &y& Elsevier]

Objective: This study examined the effect of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and several months after AMI. Background: In a human study, administration of cyclosporine A at the time of acute myocardial infarction (AMI) reperfusion was associated with a smaller infarct size. However, experimental data suggest that cyclosporine A has a detrimental effect on left ventricular remodeling. Methods: 28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. Cine imaging was used to determine LV volumes, mass, ejection fraction and myocardial wall thickness in infarcted and remote non-infarcted myocardium, and late gadolinium imaging was used to determine infarct size. Results: There was a persistent reduction of the absolute infarct size at 6 months in the cyclosporine A group compared with the control group of patients (29±15 grams VS 38±14 grams; P=0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; P=0.07) in the cyclosporine A group, compared with the control group, both at day 5 and at 6 months after infarction. There was no significant difference between the two groups in either global LV mass or regional wall thickness of the remote non-infarcted myocardium at day 5 or at 6 months. Attenuation of LV dilatation and improvement of LV ejection fraction by cyclosporine A at 6 months were correlated with infarct size reduction. Conclusion: Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling [Copyright &y& Elsevier]