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Transcatheter aortic valve replacement provides results comparable to those of surgery in patients at high surgical risk, but complications can impact long-term outcomes. The Lotus valve, designed to improve upon earlier devices, is fully repositionable and retrievable, with a unique seal to minimize paravalvular regurgitation (PVR).The prospective, single-arm, multicenter REPRISE II study (REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System: Evaluation of Safety and Performance) evaluated the transcatheter valve system for treatment of severe symptomatic calcific aortic valve stenosis.Patients (n = 120; aortic annulus 19 to 27 mm) considered by a multidisciplinary heart team to be at high surgical risk received the valve transfemorally. The primary device performance endpoint, 30-day mean pressure gradient, was assessed by an independent echocardiographic core laboratory and compared with a pre-specified performance goal. The primary safety endpoint was 30-day mortality. Secondary endpoints included safety/effectiveness metrics per Valve Academic Research Consortium criteria.Mean age was 84.4 years, 57% of the patients were female, and 76% were New York Heart Association functional class III/IV. Mean aortic valve area was 0.7 ± 0.2 cm(2). The valve was successfully implanted in all patients, with no cases of valve embolization, ectopic valve deployment, or additional valve implantation. All repositioning (n = 26) and retrieval (n = 6) attempts were successful; 34 patients (28.6%) received a permanent pacemaker. The primary device performance endpoint was met, because the mean gradient improved from 46.4 ± 15.0 mm Hg to 11.5 ± 5.2 mm Hg. At 30 days, the mortality rate was 4.2%, and the rate of disabling stroke was 1.7%; 1 (1.0%) patient had moderate PVR, whereas none had severe PVR.REPRISE II demonstrates the safety and effectiveness of the Lotus valve in patients with severe aortic stenosis who are at high surgical risk. The valve could be positioned successfully with minimal PVR. (REPRISE II: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Evaluation of Safety and Performance; NCT01627691).

ATP-dependent potassium ([Formula: see text]) channels play a role in the infarct size-limiting effect of preconditioning in pigs. We previously demonstrated that preconditioning shortens monophasic action potential duration (MAPD) and accelerates the time to ventricular fibrillation (VF) during a prolonged ischemia in pigs. We sought to determine whether the mechanism of the reduced time to VF in preconditioned pigs is a consequence of[Formula: see text] channel activation. Pigs underwent 40 min of coronary occlusion and 2 h of reperfusion. Before this, animals received either no intervention (control), 10 min of ischemia and 10 min of reperfusion (preconditioned), or an intravenous infusion of nicorandil, a [Formula: see text] channel opener. Additional control, preconditioned, and nicorandil-treated pigs were pretreated by glibenclamide, an antagonist of[Formula: see text] channels. Because 1) the[Formula: see text] channel activator nicorandil did not produce shorter time to VF, 2) the[Formula: see text] channel inhibitor glibenclamide did not block the acceleration of VF by preconditioning, and 3) there was no relationship between time to VF and infarct size or MAPD, the major conclusion is that reduced time to VF in preconditioned animals is not a consequence of [Formula: see text] channel activation.

International audience; We investigated the ability of 16-slice computer tomography (CT) to discriminate any restenosis after left main coronary artery stenting in 29 consecutive patients. CT was able to detect all stents and analyze the lumen properly in 27 of 29 cases. With the exception of arrhythmic or heavily calcified segments, multislice CT provides a noninvasive alternative to conventional coronary angiography in the follow-up of left main angioplasty with stenting.

Background— There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. Methods and Results— The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P =0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P =0.75). Reclassification safety was preserved in high-risk patients. Conclusion— This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

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.

Preconditioning protects the rat heart from ventricular arrhythmias. However, the mechanism of this beneficial effect and its existence in large animal models remain unknown. We submitted 49 pigs to 40 min of left anterior descending coronary occlusion and 2 h of reperfusion and assessed the incidence of ventricular fibrillation (VF) and time to VF. Monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were measured throughout the experiment. Preconditioning significantly reduced infarct size but failed to reduce the incidence of VF either during the 40-min ischemic insult or the following reperfusion. Moreover, preconditioning accelerated the onset of VF during the prolonged ischemia; time to VF averaged 8 +/- 2 min in the preconditioned group vs. 18 +/- 2 min in the control group (P < 0.05). This premature peak of VF in preconditioned hearts was associated with a significant decrease of VFT and shortening of MAPD. This suggests that preconditioning does not limit the incidence of VF in the pig model. Rather, preconditioning decreases the time to VF in this species, likely through lowering of the VFT and shortening of the action potential duration.

PLATFORM showed that use of fractional flow reserve derived from CT angiography (FFRCT) instead of planned invasive coronary angiography (ICA) dramatically reduces the rate of ICA showing no obstructive coronary artery disease (CAD; 12% vs 73%; core lab determined), with similar adverse events and

A 56-year–old male nonsmoker with high blood pressure was referred for a first acute coronary syndrome in the lateral territory. Coronarography identified the culprit lesion on the circumflex artery. The left anterior descending artery (LAD) showed diffuse atherosclerosis and was further explored by 40-MHz intravascular ultrasound (IVUS; baseline). Ten months later, angina recurred, without circumflex artery restenosis; an LAD plaque (P4, among the 5 plaques ultimately detected) was detected and managed medically (Figure 1). Because the patient developed Canadian Cardiovascular Society (CCS) class 3 angina, this single stenosing LAD lesion was treated by bare-metal stenting at 22 months of follow-up. Symptoms resolved, but 1 year later (at …

A b s t r ac t Background The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone. Methods In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary endpoint event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P

Antiplatelet agents have been extensively used in acute coronary syndromes and improve clinical outcome in STEMI patients. Previous experimental studies of the impact of antiplatelet agents on infarct size have been equivoqual. We questioned whether clopidogrel might reduce infarct size in STEMI patients, independently of any antithrombotic effect, by activating a post-conditioning-like myocardial protection. We retrospectively analyzed three recent controlled, randomized, proof of concept clinical trials aimed at determining whether PCI post-conditioning might attenuated infarct size in STEMI. We addressed whether clopidogrel (300–600 mg before angioplasty) might have influenced infarct size using a multivariable linear regression analysis with infarct size as the continuous outcome variable and age, clopidogrel and GP IIb/IIIa inhibitors, post-conditioning, area at risk, ischemia time, coronary thrombectomy and final TIMI flow, as covariates. In this population of 88 STEMI patients, ischemic post-conditioning and clopidogrel administration were the only two therapeutic independent predictors of the final infarct size as determined by cardiac enzymes release (p = 0.005 and p < 0.0001, respectively) This retrospective analysis supports the proposal that clopidogrel attenuates lethal reperfusion injury.

Objectives This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infarction (STEMI). Background Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. Methods Fifty patients with STEMI were randomly assigned to either a control or post-conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. Results The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post-conditioning was associated with smaller infarct size (13 ± 7 g/m2 vs. 21 ± 14 g/m2; p = 0.01) and creatine kinase peak serum level (median [interquartile range]: 1,695 [1,118 to 3,692] IU/l vs. 3,505 [2,307 to 4,929] IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 ± 16 g/m2 vs. 34 ± 18 g/m2; p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. Conclusions This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI. (Post Cond No Reflow; NCT01208727 )

We read with interest the paper by Sen et al. ([1][1]) proposing a new adenosine-independent index of stenosis severity. It is suggested that negating the need for adenosine-induced hyperemia ([2][2]) would increase adoption because of the time savings and reduction in side effects. This sounds like

Myocardial infarction is frequently developed in canine and porcine models but exceptionally in non-human primates. The aim of this study was to develop a minimally invasive myocardial ischemic/reperfusion model in the monkey intended to be combined with imaging techniques, in particular myocardial contrast echocardiography (MCE). A balloon-tipped catheter was advanced via the femoral artery into the left anterior descending artery (LAD) under fluoroscopic guidance in ten anaesthetized male rhesus monkeys (Macaca mulatta). The balloon was inflated to completely occlude the vessel. Coronary angiography (CA) was performed to control the reality of the LAD occlusion/reperfusion. The ischemia period was followed by 3-6 h of reperfusion. Myocardial perfusion was evaluated during ischemia and at reperfusion by MCE using a novel ultrasound contrast agent (BR38). Occlusion was successfully induced during 18-50 min in nine out of the ten evaluated monkeys. ST segment elevation indicated myocardial ischemia. MCE showed complete transmural arrest of myocardial blood flow during the ischemia period and no persistent microvascular perfusion defects during reperfusion. A minimally invasive closed-chest model was successfully developed for creating myocardial ischemia in the rhesus monkey (Macaca mulatta). This technique could have an important role in mimicking acute coronary syndrome under physiologically and ethically-acceptable conditions. MCE provides non-invasively information on myocardial perfusion status, information not available from CA.

The major objective of the treatment of ST elevation myocardial infarction (STEMI) patients is to reduce infarct size, which is the major prognostic factor in this population. Most of the progress has consisted in improving reperfusion therapy, both by opening as quickly as possible and by preventing reocclusion of the culprit coronary artery. Basic science research used in well-described animal models allowed to clearly establish the major determinants of infarct size, i.e., area at risk, collateral flow, duration of ischemia, and timing of the protective intervention with respect to reflow. Recent reports have proven that lethal reperfusion injury exists, that it is of significant importance, and that it can be prevented by protective interventions applied immediately before reflow. Therefore, after taking care of the vessel, it is now time to better protect the muscle against lethal reperfusion injury. In spite of several past negative infarct size reduction studies, recent proof-of-concept studies have shown that infarct size reduction is possible in STEMI patients, at least in part because the major determinants of infarct size have been taken into account. Increased understanding of underlying mechanisms from animal models together with encouraging results from phase II infarct size reduction clinical trials should help us improve the design of future studies aimed at reducing infarct size in STEMI patients.

International audience; Plaque elasticity (i.e., modulogram) and morphology are good predictors of plaque vulnerability. Recently, our group developed an intravascular ultrasound (IVUS) elasticity reconstruction method which was successfully implemented in vitro using vessel phantoms. In vivo IVUS modulography, however, remains a major challenge as the motion of the heart prevents accurate strain field estimation. We therefore designed a technique to extract accurate strain fields and modulograms from recorded IVUS sequences. We identified a set of four criteria based on tissue overlapping, RF-correlation coefficient between two successive frames, performance of the elasticity reconstruction method to recover the measured radial strain, and reproducibility of the computed modulograms over the cardiac cycle. This four-criterion selection procedure (4-CSP) was successfully tested on IVUS sequences obtained in twelve patients referred for a directional coronary atherectomy intervention. This study demonstrates the potential of the IVUS modulography technique based on the proposed 4-CSP to detect vulnerable plaques in vivo.

Periodontal disease, including bone loss, is thought to be involved in coronary artery disease. Multiple complex coronary lesions relate to multifocal destabilization of coronary plaques. We investigated whether bone loss could be associated with the presence of multiple complex coronary lesions.This cross-sectional study included 150 patients with recent myocardial infarction (1 month). Multiple complex coronary lesions were determined at coronary angiography. A panoramic dental X-ray including bone loss50% was performed. Patients with no or simple complex lesions were compared to patients with multiple complex lesions.Over 20% of patients had multiple complex coronary lesions. Patients with multiple complex lesion were less likely to be women and more likely to have multivessel disease or elevated C-reactive protein (CRP) than patients with no or single complex lesion. Bone loss50% tended to be more frequent in patients with multiple complex lesions (p = 0.063). In multivariate analysis, multivessel disease, gender and CRP were associated with multiple complex lesion. Bone loss50% increased the risk of multiple complex lesion.Bone loss was associated with complex multiple coronary lesions, beyond systemic inflammation. These findings may bear important clinical implications for the prevention and treatment of coronary artery disease.

[DOI:\hrefhttps://dx.doi.org/10.1007/s00395-011-0214-810.1007/s00395-011-0214-8] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2187455621874556]; International audience; The purpose of this study was to compare the accuracy of post-reperfusion cardiac magnetic resonance (CMR) and pre-reperfusion multidetector computed tomography (MDCT) imaging to measure the size of the area at risk (AAR), using pathology as a reference technique in a porcine acute myocardial infarction model. Fifteen pigs underwent balloon-induced coronary artery occlusion for 40 min followed by reperfusion. The AAR was assessed with arterial enhanced MDCT performed during occlusion, while two different T2 weighted (T2W) CMR imaging sequences and the contrast-enhanced (ce-) CMR endocardial surface length (ESL) were performed after 90 min of reperfusion. Animals were euthanized and the AAR was assessed by pathology. Additional measurements of the myocardial water content in the AAR, remote and the AAR border zones were performed. AAR by pathology best correlated with measurements made by MDCT (R(2) = 0.88; p < 0.001) with little bias on Bland-Altman plots (bias 2.5%, SD 6.1% LV area). AAR measurements obtained by T2W STIR, T2W ACUTE sequences or the ESL on ce-CMR showed a fair correlation with pathology (R(2) = 0.72, R(2) = 0.65 and R(2) = 0.69, respectively; all p ≤ 0.001), but significantly overestimated the size of the AAR with important bias (17.4 ± 10.8% LV area; 11.7 ± 11.0% LV area; 13.0 ± 10.3% LV area, respectively). The myocardial water content in the AAR border zones was significantly higher than the remote (82.8 vs. 78.8%; p < 0.001). Our data suggest that post-reperfusion imaging methods overestimated the AAR likely due to the presence of edema outside of the boundaries of the AAR. Pre-reperfusion arterial enhanced MDCT showed the greatest accuracy for the assessment of the AAR.

AimThanks to improved technology and the advent of transcatheter aortic valve implantation (TAVI), balloon aortic valvuloplasty (BAV) has reappared in the management of high risk patients with severe aortic stenosis in a critical clinical state in three different therapeutic strategies: 1) palliative care [A] 2) bridge to surgery [B] 3) bridge to TAVI [C]. Our main objective was to assess the safety, the effiency and the pertinence of BAV.MethodsThirty six patients with severe aortic stenosis and prohibitive surgical risk (logistic Euroscore>15% or severe commorbidities) underwent 39 BAV: 8 in strategy A, 20 in strategy B, 11 in strategy C. 3 patients underwent a second BAV due to early restenosis.ResultsThere was a significant improvement of the hemodynamic parameters after BAV: the peak to peak transaortic gradient was reduced by 56% (47mmHg vs 30mmHg; p

Reperfusion therapy is the primary treatment of acute myocardial infarction and must be applied as soon as possible to limit the ischemic insult. Unfortunately, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore. Ischemic postconditioning is a powerful intervention that dramatically reduces lethal reperfusion injury. Several clinical studies using angioplasty postconditioning now support its protective effects in patients with an acute myocardial infarction. Alternatively, pharmacological postconditioning could afford comparable protection and be applied to a much larger number of patients. Indeed, the mitochondrial permeability transition pore inhibitor cyclosporine A has been shown to generate a similar protection in acute myocardial infarction patients. Future large-scale trials are needed to determine whether angioplasty or pharmacological postconditioning may improve clinical outcome in STEMI patients.

The design of targeted ultrasound contrast agents for molecular imaging of myocardial ischemia-reperfusion (IR) requires the availability of an adequate in vivo model in a species in which cross reactivity with the target occurs. P-selectin (Psel) is an activation-dependent endothelial receptor that supports rapid and reversible cell adhesion in a flowing system. Together with E- and L-selectins it constitutes the selectin family of adhesion molecules. We investigated the myocardial expression of selectins in a closed chest minimally invasive monkey myocardial IR model. Catheter-based occlusion (30-50 min) followed by reperfusion (3 or 5 h) of left anterior descending artery (LAD) was performed in anesthetised monkeys. At the end of each procedure animals were killed, and their hearts were excised. The tissues were analyzed immunohistochemically using an anti-human Psel antibody (AK-6 clone) that cross reacts with rhesus monkey. Histopathological features confirm the presence of IR injuries in myocardial tissues. There was significant increase in the Psel expression in vessels from the IR areas. However, significantly higher Psel immunoreactivity was also seen in areas which are distant from IR injuries.

The potential advantages of percutaneous femoral access over a surgical approach are easier recovery and lower inguinal complications rate. This technique can be an asset in disabled patients with high risk of decubitus complications or in surgically challenging patients (obesity). We describe percutaneous access for mitral and aortic minimally invasive valvular interventions in 156 patients (transcatheter aortic valve implantation, n = 40; and minimally invasive cardiac surgery, n = 116). Severe complications, in two transcatheter aortic valve implantation (TAVI) patients (one retroperitoneal bleeding and one massive superficial bleeding) and in three minimally invasive patients (two retroperitoneal bleeding and one arteriovenous fistula), occurred duringfirst 50 patients versus 0 among 106 following patients (p = 0.01). Percutaneous access is possiblefor innovativecardiac interventions, but severe complications can occur, especially duringthe learning curve,with seriousconsequences in high operative risk patients, urging highest caution when initiating this innovative approach. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Aims: Angiographic analysis of left main coronary artery (LMCA) stenosis can be hindered by the lack of any reference segment when the LMCA is short or there is diffuse atheroma. Fractal geometric law (FGL) enables the theoretic diameter of one bifurcation vessel to be calculated from those of the other two (Dmother=0.678 * (D daughtr1 +D daughter2 ). Applied to the LMCA, the FGL can help the quantification of stenoses. Methods and results: Fifty-two patients with angiographically mild focal LMCA disease (n=14) or normal to nearly normal LMCA (n=38) who had undergone intravascular ultrasound (IVUS) were included. IVUS analysis confirmed all 14 focal stenoses (group C); of the 38 angiographically normal patients, however, 10 were found to present diffuse LMCA disease (group B), the remaining 28 showing a truly healthy LMCA (group A). LMCA stenosis in groups A,B and C was respectively 3%,4% and 42% on usual quantitative coronary angiography(QCA) and 5%, 31% and 43% on QCAfractal applying the FGL. In cases of diffuse atheroma, the FGL corrected the underestimation of LMCA diameter, which averaged 1.2 mm. Conclusions: Angiographic underestimation of LMCA stenosis can be corrected by applying the FGL to obtain a theoretic LMCA diameter, thereby unmasking any diffuse atherosclerotic LMCA disease, or to quantify focal stenosis more precisely where the adjacent segments are also pathological.

Fractional flow reserve measurement is based upon achieving maximum hyperemia. A 40 microg intracoronary (IC) adenosine bolus sometimes seems insufficient, and we therefore sought to assess the possible role of 100-150 microg boli in routine.108 intermediate (49+/-16%) stenoses were consecutively studied with 6F catheters. A history of myocardial infarction in the territory of the explored artery or myocardial hypertrophy were the exclusion criteria. Mean FFR was 0.82+/-0.12 with a 40 microg adenosine bolus and decreased to 0.80+/-0.12 and 0.80+/-13 respectively with 100microg and 150 microg boli (P0.001 vs 40microg in both cases; 100 vs 150 microg, NS). The 40 microg bolus failed to diagnose 8 out of 30 (27%) significant stenoses (i.e., final FFR0.75). The large boli led to 12 (11%) transient asymptomatic and spontaneously resolving AV blocks without other side-effects.FFR underestimated a quarter of intermediate stenoses with the currently used 40microg IC adenosine bolus. A large bolus up to 150 microg appears to be accurate and safe for routine FFR measurement.

Objectives This study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction. Background In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. Methods Twenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size. Results There was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 ± 15 g vs. 38 ± 14 g; 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 group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction. Conclusions Cyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728 )

assessing theeffect of abciximab delivered via an intracoronary route duringprimary percutaneous coronary intervention for limiting microvas-cular obstruction and infarct size on magnetic resonance imaging inST-elevation myocardial infarction. However, we are concerned bya potential methodological bias, because unfortunately the areas atrisk were not assessed. Area at risk could by itself explain up to 50%of infarct-size variability in experimental studies.

Background and Purpose Although brain embolism is a uncommon complication of myocardial infarction, sequential treatment of cerebral and coronary artery occlusion within a 4-hour time window is unusual. Summary: of case A 60 year-old man experienced successful intravenous recombinant thrombolysis (tPA) for acute middle cerebral artery (MCA) occlusion followed by efficient angioplasty stenting of a troponin-negative coronary occlusion which, while painless, involved clear electrocardiographic abnormalities. Both pathologies were treated within a 4-hour time window. Conclusion Acute brain and heart ischemia may be successfully treated within a 4-hour time window, thanks to an efficient multidisciplinary approach.

BACKGROUND Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

International audience; OBJECTIVE: Intravascular ultrasound (IVUS) is a cornerstone tool for the diagnosis of plaque rupture (PR) but is usually used secondary to the suspicion of PR on angiography; the true incidence of PR may therefore be overestimated. We sought to evaluate predictors of angiographic diagnosis of PR using a non-angiographically driven IVUS examination. METHODS AND RESULTS: Diagnosis of PR on IVUS required agreement between two operators blinded to the results of angiography. Any irregular lesion with ulceration, flap or aneurysm on a qualitative angiogram was considered suspicious for PR. IVUS-detected PR and non-PR lesions were compared with the corresponding angiograms. A total of 224 distinct (ruptured or non-ruptured) lesions were detected by IVUS in 65 patients; 49 of the 105 IVUS-detected non-culprit PRs were suspected on angiography. The positive and negative predictive values for correct angiographic diagnosis of PR were 96% and 61%, respectively. Proximal coronary location, wide cavity, and counterflow rupture were strong predictors of correct angiographic diagnosis, enabling four specific angiographic patterns to be identified using three-dimensional IVUS PR reconstruction. CONCLUSION: Against IVUS as the gold standard, angiographic diagnosis of PR showed good specificity but low sensitivity. However, better angiographic diagnosis should enable medical treatment to be optimized, especially with respect to statin therapy.

International audience; In a vulnerable plaque (VP), rupture often occurs at a site of high stress within the cap. It is also known that vessels do not become free of stress when all external loads are removed. Previous studies have shown that such residual stress/strain (RS/S) tends to make the stress distribution more uniform throughout the media of a normal artery. However, the influence of RS/S on the wall stress distribution in pathological coronaries remains unclear. The aim of this study was to investigate the effects of RS/S on the biomechanical stability of VPs. RS/S patterns were studied ex vivo in six human vulnerable coronary plaque samples. Because the existence of RS/S can only be assessed by releasing it, the opening angle technique was the experimental approach used to study the geometrical opening configurations of the diseased arteries, producing an arterial wall in a near-zero stress state. Reciprocally, these opening geometries were used in finite element simulations to reconstruct the RS/S distributions in closed arteries. It was found that the RS/S 1) is not negligible, 2) dramatically affects the physiological peak stress amplitude in the thin fibrous cap, 3) spotlights some new high stress areas, and 4) could be a landmark of the lipid core's developmental process within a VP. This study demonstrates that plaque rupture is not to be viewed as a consequence of intravascular pressure alone, but rather of a subtle combination of external loading and intraplaque RS/S.

Drug eluting stent (DES) thrombosis may be triggered by different phenomenon that require specific treatment and can vary according to the device properties. However, angiography alone is frequently limited to correctly identify these mechanisms. The present work aimed to investigate and compare the

We aimed to investigate the determinants and outcomes of multiple complex lesions (MCLs) on coronary angiography in patients with an acute myocardial infarction.One thousand one hundred fifty-two consecutive nonselected myocardial infarction patients who underwent coronary angiography within 24 hours after admission were analyzed. A complex lesion was defined by the presence of thrombus, ulceration, irregular plaque, and flow impairment. Patients withor = 1 complex lesion were considered with single complex lesion (SCL), and patients with1 complex lesions with MCLs.Multiple complex lesions were identified in 360 patients (31%). Patients from the MCL group were older and had a higher rate of cardiovascular risk factors but were less likely to be smokers when compared with the SCL group. Patients with MCLs were more likely to have altered left ventricular ejection fraction and multivessel disease and showed a trend toward an increased median time delay to revascularization (360 vs 285 minutes; P = .070). Moreover, the C-reactive protein (CRP) plasma levels increased with the number of CLs. By multivariate analysis, multivessel disease and CRP level were associated with the presence of MCLs. When compared with the SCL group, patients with MCLs had a higher risk of inhospital cardiogenic shock (18% vs 11%; P = .005) and 30-day mortality (11% vs 6%; P = .002). At 1-year follow-up, the presence of MCLs was an independent predictive factor of death.This study shows that the presence of MCLs is associated with worse outcomes and that risk factors such as CRP are able to identify patients at a high risk for MCLs.

Diagnosis and prognosis of coronary artery atherosclerosis evolution currently rely on plaque morphology and vessel stenosis degree. Such information can accurately be assessed with intravascular ultrasound (IVUS) imaging. A severe complication of coronary artery atherosclerosis is thrombosis, a consequence of plaque rupture or fissure, which might lead to myocardial infarction and sudden ischemic death. Plaque rupture is a complicated mechanical process, correlated with the plaque morphology, composition, mechanical properties and with the blood pressure. Extracting information on the plaque local mechanical properties may reveal relevant features about plaque vulnerability. Accordingly, endovascular elastography (EVE) was introduced to complement IVUS for investigating coronary artery diseases. In this article, in vivo elastographic data are reported for three patients (patient 1, patient 2 and patient 3) who were diagnosed with severe coronary artery stenoses. Time-sequence radio-frequency (RF) data were acquired, in the minutes preceding angioplasty, using an ultrasound scanner working with a 30 MHz mechanical rotating single-element transducer. The elastograms of the radial strain and radial shear distributions within the vessel wall were computed from pairs of successive RF images using the Lagrangian estimator (LE). A hard atherosclerotic plaque (low radial strain and shear) was identified in patient 1. High radial strain and shear values in the plaque areas for patient 2 and patient 3 suggested the presence of lipid cores (soft materials), known to be prone-to-rupture sites when located close to the lumen. To conclude, EVE allowing radial strain and shear images is an improvement over existing EVE methods that may assist IVUS in preoperative vessel lesion assessments and in endovascular therapy planning.

The aim of our study was to explore some potential pleiotropic effects of atorvastatin, after stenting in the iliac arteries of normocholesterolemic rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized into either the control group (standard chow, CTRL, n = 15) or the atorvastatin group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were harvested for histomorphometry and neointimal analysis [macrophages, matrix metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular smooth muscle cells, and collagen]. Atorvastatin did not induce significant histomorphometric and inflammatory modifications but reduced neointimal expression of MMP-2 with no modification of tissue inhibitor of metalloproteinase-2, and also induced higher neointimal collagen content (Ator vs. CTRL: MMP-2: 0.05 +/- 0.03 vs. 0.70 +/- 0.20, P < 0.01; collagen: 17.0+/-0.7%/mm vs. 12.0 +/- 1.2%/mm(2) P < 0.01). Atorvastatin treatment also induced a significant decrease in neointimal vascular smooth muscle cells and cellular density (respectively: 2.0 +/- 0.2 vs. 1.4 +/- 0.2, P < 0.05; 5406 +/- 241 nuclei/mm(2) vs. 4402 +/- 163 nuclei/mm(2), P < 0.001). Our study provides new insights into the field of MMP response to stenting and the effects of statin therapy, which could have important implications in the field of in-stent restenosis.

Diagnosis and prognosis of coronary artery atherosclerosis evolution currently rely on plaque morphology and vessel stenosis degree. Such information can accurately be accessed with IntraVascular UltraSound (IVUS) imaging. A severe complication of coronary artery atherosclerosis is thrombosis, a consequence to plaque rupture or fissure, which might lead to myocardial infarction, and sudden ischemic death. Plaque rupture is a complicated mechanical process, correlated with plaque morphology, composition, mechanical properties and with the blood pressure and its long term repetitive cycle. Extracting information on the plaque local mechanical properties and on the surrounding tissues may thus reveal relevant features about plaque vulnerability. According to that, EndoVascular Elastography (EVE) was introduced as a complementary tool to IVUS in the process of coronary artery disease investigations. In this paper, in vivo elastographic data are reported for three patients who were diagnosed with severe coronary artery stenoses. The radio-frequency (RF) data were acquired, in the minutes preceding angioplasty, using a CVIS (ClearView, CardioVascular Imaging System Inc.) ultrasound scanner working with a 30 MHz mechanical rotating single-element transducer. Due to the blood flow pulsation, the vascular tissue was naturally compressed/dilated. The elastograms, or radial strain distributions inside the vessel wall, were computed offline using the Lagrangian Speckle Model Estimator (LSME). This model-based approach considers the speckle as a material property that is, on average, conserved with tissue motion. According to that, tissue mechanical parameters (namely the strain tensor) were inferred from the speckle kinetics. The results showed the potential of the LSME to characterize and to distinguish coronary atherosclerotic plaques from the normal vascular tissue. Namely, a hard atherosclerotic plaque was detected for one patient (PAT1), whereas high strain values in the plaque region suggested the potential presence of a lipid core for PAT2. In conclusion, these results confirm that EVE might be a very relevant clinical tool to support IVUS echograms in the characterization of coronary artery. Nevertheless, further investigations are required to fully state on the potential of the method to predict the vulnerability of coronary artery atherosclerotic plaques.

Background: Several testing options are available to detect asymptomatic coronary artery disease (CAD). Dobutamine stress echocardiography (DSE) has been reported to increase the sensitivity and specificity of stress testing to detect CAD. Most studies concerned patients with known or suspected CAD who have a high pretest probability of disease. We aimed to perform a preliminary evaluation of DSE in atherothrombotic stroke. Methods: Patients with transient ischemic attack or nondisabling ischemic stroke attributable to an atherothrombotic source were prospectively recruited. Patients with a history of angina pectoris or electrocardiographic signs of previous myocardial infarction were excluded. DSE was considered positive when regional reduction or deterioration of myocardial thickening developed in 1 segment. Coronary angiography was performed in patients with positive DSE. Results: Sixty-four patients were recruited. Analysis of DSE was possible in 60 patients. Overall the test provided clinically useful information in 60/64 patients studied (>90%). DSE was positive in 9 patients (15%). Coronary angiography was performed in 8 patients, high-grade focal lesions were found in 3 patients, and 5 patients showed diffuse atheroma. Univariate logistic regression analysis showed that the main factor predictive of a positive DSE was the presence of an aortic arch atheroma (p = 0.003). Multivariate logistic regression analysis showed that two factors had an independent predictive value of positive DSE: aortic arch atheroma (p = 0.007) and dyslipidemia (p = 0.09). Conclusion: DSE may improve prevention of further vascular events in patients with an atherothrombotic source of ischemic stroke. This screening may be of particular benefit to patients with an aortic arch atheroma.

The impact of metabolic syndrome after acute myocardial infarction (AMI) has not yet been studied. In a population-based sample of patients with AMI, we sought to determine the prevalence of metabolic syndrome in patients with AMI, its impact on hospital outcomes, and to assess the relative influence of each of the components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III definition of metabolic syndrome on the risk of death and heart failure.A total of 633 unselected, consecutive patients hospitalized with AMI were categorized according to the NCEP ATP III metabolic syndrome criteria (presence of/=3 of the following: hyperglycemia; triglyceride level/=150 mg/dL [/=1.7 mmol/L]; high-density lipoprotein cholesterol level40 mg/dL [1.04 mmol/L] in men and50 mg/dL [1.30 mmol/L] in women; blood pressure/=130/85 mm Hg; and waist circumference102 cm in men or 88 cm in women).Among the 633 patients, 290 (46%) fulfilled the criteria for metabolic syndrome. Patients with metabolic syndrome were older and more likely to be women. Acute myocardial infarction characteristics and left ventricular ejection fraction rates were similar for both groups. In-hospital case fatality was higher in patients with metabolic syndrome compared with those without, as was the incidence of severe heart failure (Killip classII). In multivariate analysis, metabolic syndrome was a strong and independent predictor of severe heart failure, but not in-hospital death. Analysis of the predictive value of each of the 5 metabolic syndrome components for severe heart failure showed that hyperglycemia was the major determinant (odds ratio, 3.31; 95% confidence interval, 1.86-5.87).In an unselected population of patients with AMI, the prevalence of metabolic syndrome was high. Metabolic syndrome appeared associated with worse in-hospital outcome, with a higher risk of development of severe heart failure. Among metabolic syndrome components, hyperglycemia was the main correlate of the risk of development of severe heart failure during AMI.

To the Editor: In acute-phase myocardial infarction (AMI), Sano et al1 recently showed a C-reactive protein (CRP) concentration in excess of 3 mg/L to be closely correlated with intravascular ultrasound (IVUS) detection of a ruptured atherosclerotic plaque at the culprit lesion site. The authors concluded that such CRP elevation probably reflected inflammation caused by the plaque rupture. Certain limitations are to be noted, which affect the significance of their study, as follows. 1. CRP was elevated in >90% of patients presenting with AMI preceded by unstable angina.2 Other authors found CRP elevation in the first 6 hours of AMI, with troponin T levels remaining normal.3 Now, 40% of the Sano et al1 population had preinfarction angina and one third …

International audience; BACKGROUND: A 'thin' fibrous cap atheroma is the typical morphological characteristic of vulnerable plaque. Yet the very pathological studies that have provided these descriptions have also shown the actual prediction of plaque rupture to be rather less exact. Other relevant characteristics must be involved in the mechanisms of plaque rupture--blood pressure loading (P) and the material properties of the soft atheromatous core--as predictors of the distribution of the peak circumferential stress (PCS) locations. METHODS AND RESULTS: We used a computational structural analysis based on three typical in-vivo intravascular ultrasound images of fibrous cap atheroma in which we decreased the cap thickness (CTh). With different soft atheromatous core Young's moduli (Ecore), 414 simulations were performed under eight different physiological loading blood pressures. The transition from plaque stability to plaque instability was defined by a threshold of 300 kPa and is a feature of vulnerability. It was found that (1) irrespective of plaque geometry and composition, CTh < 60 microm exposed the plaque to PCSs in excess of 300 kPa; (2) the exponential variations in PCS with change in CTh and Ecore values show that very slight structural changes are enough to tilt a vulnerable plaque from stability to instability or vice versa; and (3) the relationship between P and PCS is proportional with P acting as trigger or as protector. CONCLUSION: The present study shows why, in clinical practice, mere morphological detection by imaging techniques of thin-cap fibro-atheroma is not in itself enough for the prediction of future rupture.

Myocardial stunning, a transient contractile dysfunction that appears following a brief period of ischemia, is at least partly due to the production of oxygen-derived free radicals. The objective of the present study was to determine whether the Ginkgo biloba extract EGb761, which has antioxidant properties in vitro, can attenuate myocardial stunning in vivo. Forty-seven anesthetized open-chest farm pigs underwent 10 min of occlusion of the left anterior descending coronary artery (LAD), followed by 3 hours of reperfusion. They were pretreated with either physiological saline, 100 mg or 300 mg of EGb 761 (Protocol I) or 3 mg or 9 mg of ginkgolide B (GkB) (Protocol II). Contractile function was assessed by sonomicrometry. Both doses of EGb 761 significantly improved recovery of contractile function in the reperfused myocardium with segment shortening averaging 23 +/- 5 % of baseline values at 3 hours post-reflow in controls versus 81 +/- 10 % and 57 +/- 12 % in the EGb100 and EGb300 groups, respectively (p0.05 vs control in both cases). In contrast, neither dose of GkB improved functional recovery during reperfusion. ESR experiments revealed that EGb761 resulted in a 59 % decrease in myocardial spin-adduct release during reperfusion (p0.05 versus control and GkB groups). A significant 28 % decrease (p0.05 vs control group) was also obtained in GkB-treated animals. These results indicate that EGb 761 can attenuate myocardial stunning following a brief ischemic insult in the in situ pig heart by an effect that involves a decrease in the formation of free radicals. As the effect of EGb 761 on functional recovery cannot be explained by the presence of GkB, the beneficial action of the extract on myocardial stunning likely involves complementary effects of both its non-ginkgolide and ginkgolide constituents.

Beware so long as you live of judging men by their outward appearance., —Jean de la Fontaine ([1][1]) Following Gould and Lipscomb's seminal work in the 1970s, 50% coronary stenosis was shown to be liable to reduce arterial blood flow in hyperemia: that is, in a situation pragmatically equivalent

The myocardial area at risk (AAR) is a major determinant of infarct size. Which imaging technique is the most appropriate to accurately measure its size remains debated.