Frédéric Cransac

Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Normal Ejection Fraction Is Associated With Severe Left Ventricular Dysfunction as Assessed by Speckle-Tracking Echocardiography: A Multicenter Study

Background— Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. Methods and Results— In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ⩽35 mL/m2, low gradient as a mean gradient ⩽40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm2 versus 0.86±0.14 cm2), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m2), and worse longitudinal left ventricular function (basal longitudinal strain=−11.6±3.4 versus −14.8±3%; P<0.001 for all). Conclusions— LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

Delayed Postconditioning in the Mouse Heart In Vivo

Background— Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size. Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients. Methods and Results— Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR60′). Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (&Dgr;t) after reopening of the coronary artery (&Dgr;t=10 seconds, 1, 5, 10, 15, 20, 30, and 45 minutes; PostC&Dgr;t). Infarct size/area at risk was reduced by 71% in PostC&Dgr;1 compared with IR60′ mice (P=5×10−6). There was a linear correlation (r2=0.91) between infarct size and &Dgr;t, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when &Dgr;t time increased. The protective effect of PostC&Dgr;1 and PostC&Dgr;15 was still effective when the duration of reperfusion was prolonged to 24 hours (IR24 hours; PostC&Dgr;1 and PostC&Dgr;15 versus IR24 hours, P=0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release. Conclusions— This study in our in vivo mouse model of myocardial IR shows for the first time that delaying the intervention of postconditioning to 30 minutes does not abrogate the cardioprotective effect of postconditioning. This finding provides evidence that the time window of protection afforded by postconditioning may be larger than initially reported.

Can troponin elevation predict worse prognosis in patients with acute pericarditis

INTRODUCTION Myopericarditis are common in clinical practice: up to 15% of acute pericarditis have a significant myocardial involvement as assessed by biological markers. This prospective, bicentric study is aimed at describing a myopericarditis population, the clinical and MRI follow-up, and search for prognosis markers. PATIENTS AND METHODS Between May 2005 and September 2007, 103 patients hospitalised for acute pericarditis were prospectively enrolled. Physical examination, ECG, echocardiography, biological screening and cardiac MRI, in case of myopericarditis defined as acute pericarditis with troponin I elevation, were performed. Between December 2007 and July 2008, patients were contacted for new clinical and MRI evaluation. RESULTS Among the initial population of 103 patients admitted for acute pericarditis, 14 myopericarditis and 38 pericarditis were included. Compared with pericarditis, the myopericarditis group was associated with the following features: younger age (34.9 years [95% CI 28.3-41.2]; p=0.01), ST-segment elevation (nine patients between 14; p=0.03), higher troponin I (7.3 microg/L [95% CI 4.4-10.2]; p<10(-4)) and lower systemic inflammation (CRP peak 38.1mg/L [95% CI 7-69.2]; p=0.01). In the case of myopericarditis, infectious etiologies were predominant (12 patients among 14; p=0.002) and patients stayed longer in hospital (5.8 days [95% CI 4.7-6.8]; p=0.01). Follow-up showed no difference in terms of functional status (p=0.3) and global complications (p=0.9) between paired myopericarditis and pericarditis. Nevertheless, cardiac mortality was higher for myopericarditis (p=0.04). MRI follow-up showed myocardial sequelae without clinical impact. CONCLUSION Myopericarditis significantly distinguished from pericarditis. Three years follow-up showed no difference in terms of global complications but a higher cardiac mortality for myopericarditis. MRI myocardial lesions did not develop into symptomatic sequelae.

Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury

Background— Apoptosis has been described extensively in acute myocardial infarction and chronic heart failure. Because Daxx (death-associated protein) appears to be essential for stress-induced cell death and acts as an antisurvival molecule, we tested the hypothesis that Daxx is involved in myocardial ischemia/reperfusion–induced cell death in vivo. Methods and Results— Transgenic mice overexpressing a dominant-negative form of Daxx (Daxx-DN) under the control of the &bgr;-actin promoter and control wild-type mice underwent an ischemia/reperfusion protocol: 40 minutes of left coronary artery occlusion and 60 minutes of reperfusion. Area at risk and infarct size were measured after dual staining by triphenyltetrazolium chloride and phthalocyanine blue dye. Apoptosis was measured in the ischemic versus the nonischemic part of the left ventricle by terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end labeling staining, enzyme-linked immunosorbent assay, and Western blotting of caspase-3, caspase-8, and poly(ADP-ribose) polymerase. The mitogen-activated protein kinase status was investigated by Western blot analysis. Comparison between groups was assessed by ANOVA or Student t test (statistical significance: P<0.05). Left ventricle tissues from transgenic mice expressed Daxx-DN at the protein level. Area at risk/left ventricle values were comparable among groups. Infarct size/area at risk was 45% reduced in Daxx-DN versus wild-type mice (P<0.001). This cardioprotection was maintained for a 4-hour reperfusion. Ischemia/reperfusion-induced apoptosis was significantly decreased and ERK1/2 prosurvival pathway was activated in ischemic Daxx-DN hearts. Conclusions— Our study clearly indicates that Daxx participates in myocardial ischemia/reperfusion proapoptotic signaling in vivo.

Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST-segment elevation myocardial infarction treated by primary coronary intervention

Purpose: Cardiac biomarkers including troponins are the cornerstone of the biological definition of acute myocardial infarction. New high-sensitivity cardiac assays determining troponin T (hs-cTnT) as well as I ((hs-cTnI) from Abbott and s-cTnI from Siemens) raise concerns because of their unclear kinetics following the peak. Aims: This study aims to compare kinetics of creatine kinases, hs-cTnT, hs-cTnI and s-cTnI in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Methods: We prospectively studied 106 consecutive patients admitted in our institution for STEMI and treated by percutaneous coronary intervention. We evaluated for all the patients simultaneously kinetics of creatine kinases, hs-cTnT (Roche) and two different cTnIs (hs-cTnI from Abbott and s-cTnI from Siemens). Modelling of kinetics was realized using mixed effects with cubic splines. Results: Kinetics of markers showed a first peak at 10.7h (8.0–12.0) for creatine kinases, 11.8h (10.4–13.3) for hs-cTnT (Roche); 11.8h (10.7–11.8) for hs-cTnI from Abbott and 10.2h (8.7–11.6) for s-cTnI from Siemens, respectively. This peak was followed by a nearly log linear decrease for hs-cTnI/s-cTnI and creatine kinases in contrast to hs-cTnT, which appeared with a biphasic shape curve marked by a second peak at 76.9h (69.5–82.8). The analysis of the decrease in percentage of the peak value at 77h showed that hs-cTnT follows a twice lower decrease than other markers. Conclusion: Kinetics of hs-cTnT, hs-cTnI and s-cTnI differ significantly with a linear decrease regarding both cTnI assays contrasting with a biphasic shape curve for hs-cTnT. This is of importance for clinical management of patients in routine settings especially in follow-up after STEMI including the suspicion of reinfarction.

Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction

Abstract Background: Cardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI). Methods: We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines. Results: Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9–12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1–99.9) vs. cTnI by 86.8% (76.6–92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9–42.9) when compared with CK that fell by 79.5% (64.3–90.7). Conclusions: Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

Intracoronary administration of darbepoetin-alpha at onset of reperfusion in acute myocardial infarction: Results of the randomized Intra-Co-EpoMI trial

BACKGROUND Several trials investigating erythropoietin as a novel cytoprotective agent in myocardial infarction (MI) failed to translate promising preclinical results into the clinical setting. These trials could have missed crucial events occurring in the first few minutes of reperfusion. Our study differs by earlier intracoronary administration of a longer-acting erythropoietin analogue at the onset of reperfusion. AIM To evaluate the ability of intracoronary administration of darbepoetin-alpha (DA) at the very onset of the reperfusion, to decrease infarct size (IS). METHODS We randomly assigned 56 patients with acute ST-segment elevation MI to receive an intracoronary bolus of DA 150 μg (DA group) or normal saline (control group) at the onset of reflow obtained by primary percutaneous coronary intervention (PCI). IS and area at risk (AAR) were evaluated by biomarkers, cardiac magnetic resonance (CMR) and validated angiographical scores. RESULTS There was no difference between groups regarding duration of ischemia, Thrombolysis in Myocardial Infarction flow grade at admission and after PCI, AAR size and extent of the collateral circulation, which are the main determinants of IS. The release of creatine kinase was not significantly different between the two groups even when adjusted to AAR size. Between 3-7 days and at 3 months, the area of hyperenhancement on CMR expressed as a percentage of the left ventricular myocardium was not significantly reduced in the DA group even when adjusted to AAR size. CONCLUSION Early intracoronary administration of a longer-acting erythropoietin analogue in patients with acute MI at the time of reperfusion does not significantly reduce IS.

Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study

Background Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). Aim The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (123I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). Patients and methods A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using 123I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. Results 123I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). Conclusion In patients with STEMI, 123I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Pericarditi acute e croniche

Le pericarditi costituiscono un vasto insieme di patologie al tempo stesso frequenti e molto eterogenee. Tra le pericarditi acute, si ricorda la frequentissima pericardite acuta benigna virale, la cui evoluzione e, il piu delle volte, favorevole. La ricerca eziologica e, generalmente, inutile; il trattamento associa antinfiammatori e colchicina. La complicanza piu frequente e la recidiva. Le forme recidivanti sono, tuttavia, piu rare. Il tamponamento e una complicanza piu rara ma un’urgenza vitale, che richiede un trattamento in estrema urgenza che associa riempimento ed evacuazione del versamento. Tra le diagnosi differenziali, i dolori toracici devono essere scrupolosamente indagati. Le miopericarditi costituiscono un’entita separata, trattata in altra sede. Le pericarditi croniche si inseriscono in un contesto del tutto differente, complicando raramente una forma inizialmente acuta. L’iter tanto diagnostico che terapeutico e complesso, basato su una serie di argomenti e su una gestione multidisciplinare.

Prevalence of obstructive sleep apnoea in acute coronary syndrome: Routine screening in intensive coronary care units

INTRODUCTION Increased evidence has shown that, despite the maximum care afforded to patients admitted with acute coronary syndromes (ACS), a residual risk of mortality remains, in which obstructive sleep apnoea (OSA) appears to be a largely undiagnosed factor, particularly in the intensive cardiac care unit (ICCU). The purpose of this study is to determine whether the systematic screening for sleep-disordered breathing (SDB) is feasible and may be recommended. The aims of our study are to determine: (1) The estimated prevalence of OSA in patients admitted to the ICCU for ACS determined by a validated, user-friendly portable screening device; (2) The feasibility of the screening in this context; (3) To assess any negative impact of OSA on the severity of ACS. PATIENTS AND METHODS This is an observational study of 101 patients admitted to the ICCU for ACS showing no clinical evidence of heart failure (HF). In the 24-72hours following admission, they underwent an overnight sleep study using a 3-channel portable screening device with automatic analysis. RESULTS Sixty-two out of the 101 patients proved positive to the screening test, and its feasibility was acceptable. OSA patients tended to have greater peak levels of hs-cTnT (3685±3576ng/L versus 2830±3333ng/L, P=0.08) than the non-OSA group. Compared with the non-OSA group, OSA patients presented more severe ACS, with a greater average GRACE score at admission of 112.2±26.3 (versus 98.4±19.2, P<0.001). In the OSA group, we found a statistically significant inverse correlation between the apnoea-hypopnea index (AHI) and the left ventricular ejection fraction (LVEF) in the linear regression analysis (r=-0.26; P=0.037). CONCLUSIONS A systematic screening of patients in the ICCU is acceptable. OSA is frequently found in the acute phase of ischaemic heart disease and its presence is associated with more severe ACS and a poorer left ventricle systolic function.