No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL NUMBER: NCT01483755.

Morphological and biomechanical aspects of vulnerable coronary plaque.

Vulnerable plaque morphology has been described by gross pathology and intravascular ultrasound, but morphological criteria cannot fully explain vulnerability, which involves four distinct factors: 1) inflammatory and biological processes; 2) geometry; 3) composition; and 4) hemodynamic stress. These last three aspects underlie the biomechanical study of vulnerable plaque. By virtue of the nature of their evolution, atherosclerotic plaques tend to be excentric, and this is a crucial morphological feature, causing circumferential stress to peak in very specific juxta-luminal locations, where it can exceed the rupture threshold of collagen, the basic constituent of arterial architecture. The lipido-necrotic core covered by a fibrous cap, formed in young plaques, is another morphological feature, which, can also increase and concentrate circumference stress in the juxta-luminal fibrous cap. The larger the lipid core, the thinner the fibrous cap and the greater is the stress. There are also inflammatory processes in such areas, which tend to reduce cap thickness. Ruptures occur when this thickness falls below 65 microns. Heart rate, blood pressure and pulse pressure are all biomechanical factors affecting vulnerable arterial walls, increasing circumferential stress and material fatigue. Vulnerable plaques are almost always associated with positive arterial remodeling. Numerical simulation has shown such so-called compensatory remodeling to be exclusively due to the healthy arc stretching in vulnerable plaques. Positive remodeling is optimal when the healthy arc is around 170 degrees, which keeps the lumen area relatively stable as long as the plaque does not exceed 40% to 50%. This mechanism does not apply to concentric plaques. In conclusion, the mechanism of vulnerable plaque rupture is highly complex and multifactorial. This complexity more or less precludes prediction in individual cases: we are in the realms of chaos theory and acute sensitivity to initial conditions. The greatest caution is therefore required in any attempt to predict rupture from diagnostic imagery, which provides only morphological data on plaque's nature.

[Myocardial bridging and coronary spasm on effort]. / Pont myocardique et spasme coronaire à l'effort.

The discovery of myocardial bridging during coronary angiographies is common. Yet these bridges are rarely the origin of acute coronary syndrome. We report the case of an active 45 year old man with no cardiovascular risk factors who had acute coronary syndrome. Emergency coronary angiography just revealed two myocardial bridges on the anterior interventricular artery which did not explain this acute episode. A subsequent second angiogram together with endocoronary echography demonstrated that there was no atheroma and a methergin test set off diffuse coronary spasm. The association of myocardial bridging and coronary spasm has only rarely been reported in the literature. We describe the clinical, therapeutic and prognostic characteristics.

Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study.

BACKGROUND: To test the hypothesis of general atherosclerotic plaque destabilization during acute coronary syndrome (ACS), the present study sought to analyze the 3 coronary arteries by systematic intravascular ultrasound scan (IVUS). METHODS AND RESULTS: Seventy-two arteries were explored in 24 patients referred for percutaneous coronary intervention after a first ACS with troponin I elevation. Fifty plaque ruptures (mean, 2.08 per patient; range, 0 to 6) were diagnosed by the association of a ruptured capsule with intraplaque cavity. Plaque rupture on the culprit lesion was found in 9 patients (37.5%). At least 1 plaque rupture was found somewhere other than on the culprit lesion in 19 patients (79%). These lesions were in a different artery than the culprit artery in 70.8% and were in both other arteries in 12.5% of these 24 patients. Complete IVUS examination of all 3 coronary axes in patients who had experienced a first ACS revealed that multiple atherosclerotic plaque ruptures were detected by IVUS; these multiple ruptures were present simultaneously with the culprit lesion; they were frequent and located (in three quarters of cases) on the 3 principal coronary trunks; and the multiple plaque ruptures in locations other than on the culprit lesion were less severe, nonstenosing, and less calcified. CONCLUSION: Although one single lesion is clinically active at the time of ACS, the syndrome seems nevertheless associated with overall coronary instability.

Influence of the morphogranulometry and hydrophobicity of talc on its antisticking power in the production of tablets.

Antisticking power varies according to the talc considered. It is difficult to define the physical properties of talc implicated in its antisticking power. In this work, different talcs were characterized and an evaluation made of their performance in reducing sticking in tablet manufacturing. Determination of the specific surface area was made by permeametry, morphogranulometric analysis by laser diffractometry using a method, which made it possible to assess the mean thickness of talc particles, and measurement of water absorption kinetics was taken to assess hydrophobicity. The relationship between the characteristics of talcs and their antisticking power was then considered. There is a correlation between the particle size of talc and surface hydrophobicity. The detaching force of tablets appears to be dependent on the basal dimension of talc.

[Morphological and functional characteristics of the culprit coronary artery in acute coronary syndrome]. / Aspects morphologiques et fonctionnels de l'artère coronaire coupable d'un syndrome coronaire aigu.

In the catheter laboratory, faced with a patient with unstable angina, the problem is not the diagnosis of epicardial coronary artery stenosis but rather the atherothrombotic complexity of the stenosis and the identification of other less stenotic lesions on angiographically normal or nearly normal segments. The authors describe two appearances with morphological analysis of the vulnerable or unstable plaque and functional analysis of coronary artery vasomotricity. Acute coronary syndromes due to a clearly stenotic atherothrombotic plaque on angiography pose no diagnostic problems. However, an acute coronary syndrome may be more difficult to assess when angiography shows only simple irregularities of the lumen or no lesions at all. In these cases, angiography is said to be normal and the coronary arteries are considered to be possibly "healthy". Evaluation of the vessels' vasomotricity is especially valuable in this context. Using pharmacological stress tests, endovascular ultrasonography is a complementary diagnostic tool which allows identification of the unstable atheromatous process or of a partial atherothrombosis masked by positive remodelling process. These tests may also indicate the optimal treatment.

[Emergent transcatheter aortic valve implantation in a patient with bicuspid aortic valve stenosis in cardiogenic shock]. / Choc cardiogénique sur bicuspidie aortique sténosante traité par remplacement valvulaire aortique percutané en urgence.

Transcatheter aortic valve implantation is a therapeutic option for high-risk patients with severe aortic valve stenosis and with cardiac symptoms. This procedure requires the preliminary evaluation by a "heart team" and presents some contraindications. We report the case of a 58-year-old man with severe bicuspid aortic valve stenosis and cardiogenic shock. In spite of contraindications and because of the failure of balloon aortic valvuloplasty, transcatheter aortic valve implantation was performed in emergency.

Tortuosity of coronary bifurcation as a potential local risk factor for atherosclerosis: CFD steady state study based on in vivo dynamic CT measurements.

The purpose of the present study was to determine whether in vivo bifurcation geometric factors would permit prediction of the risk of atherosclerosis. It is worldwide accepted that low or oscillatory wall shear stress (WSS) is a robust hemodynamic factor in the development of atherosclerotic plaque and has a strong correlation with the local site of plaque deposition. However, it still remains unclear how coronary bifurcation geometries are correlated with such hemodynamic forces. Computational fluid dynamics simulations were performed on left main (LM) coronary bifurcation geometries derived from CT of eight patients without significant atherosclerosis. WSS amplitudes were accurately quantified at two high risk zones of atherosclerosis, namely at proximal left anterior descending artery (LAD) and at proximal left circumflex artery (LCx), and also at three high WSS concentration sites near the bifurcation. Statistical analysis was used to highlight relationships between WSS amplitudes calculated at these five zones of interest and various geometric factors. The tortuosity index of the LM-LAD segment appears to be an emergent geometric factor in determining the low WSS amplitude at proximal LAD. Strong correlations were found between the high WSS amplitudes calculated at the endothelial regions close to the flow divider. This study not only demonstrated that CT imaging studies of local risk factor for atherosclerosis could be clinically performed, but also showed that tortuosity of LM-LAD coronary branch could be used as a surrogate marker for the onset of atherosclerosis.

Can we optimize our angiographic views every time? Qualitative and quantitative evaluation of a new functionality.

RATIONALE AND OBJECTIVES: For determining the optimum angulations of the x-ray beam with respect to the vascular morphology of a given patient, the authors present a solution combining a single-plane angiographic system and a dedicated procedure. METHODS: The clinical evaluation of the vessel profiling acquisitions focuses on qualitative appraisal and quantitative analysis of conventional and optimum projections. RESULTS: The qualitative evaluation demonstrates the pitfall for an operator to discern optimum from conventional projections. The 70% of preferences for vessel profiling bear witness to the constraints imposed occasionally by the optimum angulations, which may be impracticable for various reasons. However, vessel profiling yields lesions inspection at an optimum view, free of geometric foreshortening. Moreover, there is less risk of superimposition with other branches. From a quantitative standpoint, vessel profiling unveils the lesion with a length significantly longer than in conventional view. CONCLUSIONS: Vessel profiling offers a qualitative optimization of angiographic images and more exact quantitative analysis.

Risk and results of bypass grafting using bilateral internal mammary and right gastroepiploic arteries.

From January 1990 to June 1994, 240 patients (mean age, 60 +/- 10 years) underwent myocardial revascularization with the exclusive use of in situ bilateral internal mammary and right gastroepiploic arteries. Left ventricular function was normal in 34% of patients, moderately impaired in 58.5%, and severely impaired in 7.5%. The mean number of distal anastomoses was 3.5 +/- 0.7 and the rate of complete myocardial revascularization was 80%. Early mortality was 0.4%, and complications occurred in 20 patients: myocardial infarction, 1.6%; intraaortic balloon pump, 0.8%; reoperation for bleeding, 0.8%; and mediastinitis, 0.4%. Early (15th postoperative day) angiographic control of grafts was performed in 51 patients; the rate of functional and patent anastomoses was 100% for internal mammary arteries and 96% for gastroepiploic arteries. Early functional results (3 +/- 1 postoperative months) were studied in 141 patients during exercise test with medical treatment: 99% were symptom-free and 14% had ischemic modification of electrocardiograms. A 2-year postoperative functional assessment without medical treatment was performed during exercise test in 66 patients: 98% were symptom-free and 26% had ischemic modification of electrocardiograms; during the same procedure, thallium myocardial scintigraphy was obtained in 50 patients and 18 patients had moderate ischemic defect on exercise. Ischemic modifications of electrocardiograms and defects seen on thallium scintigraphy were correlated significantly with incomplete revascularization (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Late hemodynamic results after cardiomyoplasty in congestive heart failure.

Between November 1989 and September 1990, a cardiomyoplasty procedure was performed in 12 male patients with a mean age of 59 years. All patients were in New York Heart Association class III. Reinforcement cardiomyoplasty was isolated in 4 patients and associated with a cardiac procedure in 8. There were no perioperative deaths. Failure of cardiomyoplasty occurred in 5 patients because of recurrence of disabling congestive heart failure: 3 patients died late, and 2 had heart transplantation. The actuarial survival rate was 83% at 1 year and 73% at 2 years. Hemodynamic studies were done preoperatively in all patients, at 6 months postoperatively in 11 patients, at 1 year in 8, and at 2 years in 7. At the 2-year follow-up, 6 of the 7 survivors who did not have transplantation were functionally improved with reduced medical treatment. The following indices improved significantly at the 2-year evaluation compared with baseline: exercise capacity (63 +/- 13 W versus 83 +/- 17 W); left ventricular (LV) end-diastolic pressure (20 +/- 7 mm Hg versus 11 +/- 5 mm Hg); and angiographic LV ejection fraction (0.25 +/- 0.09 versus 0.40 +/- 0.15). Pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac index remained unchanged. Four patients underwent beat-to-beat analysis of LV function at 2 years; during skeletal muscle stimulation, stroke volume increased by 7% to 35% and LV end-systolic pressure, by 5% to 9%. In the 5 patients with failed cardiomyoplasty, mean pulmonary artery pressure and LV end-diastolic volume were higher preoperatively than in the 7 survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

In-vivo prediction of human coronary plaque rupture location using intravascular ultrasound and the finite element method.

BACKGROUND: Spontaneous rupture of atherosclerotic plaques is known to be involved in the mechanism leading to acute coronary syndromes. Means to detect plaques prone to rupture and predict rupture location would then be very valuable for clinical diagnosis. DESIGN: In this study, finite element (FE) analysis based on intravascular ultrasound (IVUS) images of atherosclerotic arteries was used to predict in-vivo plaque rupture locations. In four patients with coronary artery diseases, IVUS images were recorded before and after balloon angioplasty. Pre-angioplasty images were recorded after injection of ATP. This caused a brief drop of arterial blood pressure down to values of about 20 mmHg, and thus allowed the recording of the unloaded configurations of arteries used to initiate FE analysis. Plaque rupture was triggered by balloon inflation (coronary angioplasty). FE simulations were performed under physiological loading conditions. Stress distributions within the plaque and the arterial wall were determined. The corresponding stress maps are presented. RESULTS: Circumferential tensile peak stress areas were compared with plaque rupture locations on postangioplasty IVUS images. They were found to coincide in all four studied cases. CONCLUSION: Our results agreed with those reported in previous studies based on ex-vivo postnecropsic data and showed the feasibility of in-vivo prediction of atherosclerotic plaque rupture location.

Mechanical properties of coronary stents determined by using finite element analysis.

The mechanical function of a stent deployed in a damaged artery is to provide a metallic tubular mesh structure. The purpose of this study was to determine the exact mechanical characteristics of stents. In order to achieve this, we have used finite-element analysis to model two different type of stents: tubular stents (TS) and coil stents (CS). The two stents chosen for this modeling present the most extreme mechanical characteristics of the respective types. Seven mechanical properties were studied by mathematical modeling with determination of: (1) stent deployment pressure, (2) the intrinsic elastic recoil of the material used, (3) the resistance of the stent to external compressive forces, (4) the stent foreshortening, (5) the stent coverage area, (6) the stent flexibility, and (7) the stress maps. The pressure required for deployment of CS was significantly lower than that required for TS, over 2.8 times greater pressure was required for the tubular model. The elastic recoil of TS is higher than CS (5.4% and 2.6%, respectively). TS could be deformed by 10% at compressive pressures of between 0.7 and 1.3 atm whereas CS was only deformed at 0.2 and 0.7 atm. The degree of shortening observed increases with deployment diameter for TS. CS lengthen during deployment. The metal coverage area is two times greater for TS than for CS. The ratio between the stiffness of TS and that of CS varies from 2060 to 2858 depending on the direction in which the force is applied. TS are very rigid and CS are significantly more flexible. Stress mapping shows stress to be localized at link nodes. This series of finite-element analyses illustrates and quantifies the main mechanical characteristics of two different commonly used stents. In interventional cardiology, we need to understand their mechanisms of implantation and action.

Axial strain imaging of intravascular data: results on polyvinyl alcohol cryogel phantoms and carotid artery.

Mapping the local elastic properties of an atherosclerotic artery is of major interest for predicting the disease evolution or an intervention outcome. These properties can be investigated by elastography, which estimates the strain distribution within a medium in response to a stress. But because diseased arteries are highly heterogeneous, a small global deformation may result in high local strains in the softest regions. For those reasons, we use in this paper the strain estimation method we recently developed to compute elastograms of original vessel-mimicking cryogel phantoms and a fresh excised human carotid artery. This adaptive method has been effectively proved to be accurate in a wider range of strains (0-7%) than commonly used gradient-based methods, and very adapted for investigating highly heterogeneous tissues. Resulting elastograms cover a wider range of strains (0-3.5%) than all previously reported intravascular elastograms, improving the discrimination between healthy and diseased regions.

Modeling geometric artefacts in intravascular ultrasound imaging.

A model has been developed for estimating the geometric distortions in intravascular ultrasound (IVUS) imaging caused by the position of the ultrasound catheter within the artery. Geometric distortion causes degradation on cross-sectional images of the vessel wall where, for characteristic positioning of the transducer within the vessel, a circular artery is seen on IVUS images as a noncircular vessel represented by more or less complex shapes. Artefacts, therefore, have a clinical impact on the accuracy of qualitative and quantitative intravascular analyses. The main distortions are due to the inclination and the off-centered position of the transducer within the vessel. These effects are increased by two factors: first, the point of origin of the ultrasound beam does not coincide with the rotation axis of the catheter; second, in the case of a mechanical rotating transducer, the ultrasound beam is not perpendicular to the long axis of the catheter, but has an inclination such that the transducer looks forward from the emitting point. All these parameters are taken into account in the three-dimensional (3-D) geometric model developed in this paper. The model was formulated to predict the geometric deformation for artery contour of various shapes and can model artefacts during stent implantation (Finet et al. 1998). Simulations were made for various geometric configurations and compared to in vitro and in vivo IVUS images. The model results are consistent with the experimental results. Finally, the model was used for estimating the values of the geometric parameters that cause distortions on ultrasonic images.

Artifacts in intravascular ultrasound imaging during coronary artery stent implantation.

Intravascular ultrasound imaging is able to provide direct images of the stent meshwork. However, a paradoxical question remains unanswered: Why is it not possible to correct or prevent implantation defects by ultrasound-guided implantation? We postulate that these discrepancies are due to image artifacts. We performed an in vitro experiment allowing detection, physical characterization, and computerized simulations of the various aspects of these artifacts. The width of the echo of a strut is variable, dependent on its distance from the transducer. The stent strut echo orientation is variable, and depends on the position of the transducer inside the stent. The stent contour image depends on the position of the transducer. In conclusion, knowledge of these stent intravascular ultrasound image artifacts enabled us to discriminate accurately between artifacts and real stent implantation defects, and are indispensable for accurate qualitative and quantitative analyses of stents.

Ultrasound contrast agent in intravascular echography: an in vitro study.

The intravascular ultrasound image of the intraluminal contour depends on the difference between acoustic impedances of the media which create the endoluminal interface. There are several limitations to the visualization and detection of this interface. These limitations are due to artifacts encountered during image formation and to anatomical complexity. The purpose of this study is to obtain intraluminal contour enhancement using ultrasound contrast agent (UCA). Therefore, our objective was to address the feasibility of this technique by documenting the following: (i) the acoustic properties of UCA at 30 MHz; (ii) in vitro experimentation with tube or postnecrotic artery; and (iii) suitable digital processing. The images obtained with UCA (enhanced image quality) and subtracted from those without UCA provided, after simple digital processing, accurate visualization of the arterial lumen. The image obtained exhibits an even, high-contrast intraluminal edge. Such characteristics facilitate contour extraction by the automated contour detection procedures.

Artifacts in intravascular ultrasound imaging: analyses and implications.

The ability of an intravascular ultrasound catheter to give cross-sectional images of vessel walls and surrounding tissues, and the behavior of ultrasound in heterogeneous media, are at the origin of degradation of image quality. Qualitative and quantitative analyses of in vivo studies are then operator-dependent and are limited by artifacts. We investigated these limitations by an in vitro study on plexiglass phantoms and segments of fresh arteries. We used a 20 MHz transducer mounted on the tip of a 4.8 F catheter and an interventional ultrasound system. The ultrasound beam is reflected onto the rotating transducer at 600 rotations per minute (RPM), creating 360 degrees real-time images (10 images/second). We then observed, analyzed and interpreted the most specific reasons for image artifacts: geometric distortions, multiple echoes, the point spread function (PSF) of the imaging system, near-field effects, "petal-shaped" effect, and ultrasound speckle. Various practical implications have resulted from this study. Only a thorough knowledge of how to avoid some of the most obvious pitfalls will enable the user to obtain maximum benefits from intravascular ultrasound imaging, and to appreciate its limitations.

Modeling the 3D coronary tree for labeling purposes.

Coronary artery diseases are usually revealed using X-ray angiographies. Such images are complex to analyze because they provide a 2D projection of a 3D object. Medical diagnosis suffers from inter- and intra-clinician variability. Therefore, reliable software for the 3D reconstruction and labeling of the coronary tree is strongly desired. It requires the matching of the vessels in the different available angiograms, and an approach which identifies the arteries by their anatomical names is a way to solve this difficult problem. This paper focuses on the automatic labeling of the left coronary tree in X-ray angiography. Our approach is based on a 3D topological model, built from the 3D anthropomorphic phantom, Coronix. The phantom is projected under different angles of view to provide a data base of 2D topological models. On the other hand, the vessel skeleton is extracted from the patient's angiogram. The algorithm compares the skeleton with the 2D topological model which has the most similar vascular net shape. The method performs in a hierarchical manner, first labeling the main artery, then the sub-branches. It handles inter-individual anatomical variations, segmentation errors and image ambiguities. We tested the method on standard angiograms of Coronix and on clinical examinations of nine patients. We demonstrated successful scores of 90% correct labeling for the main arteries and 60% for the sub-branches. The method appears to be particularly efficient for the arteries in focus. It is therefore a very promising tool for the automatic 3D reconstruction of the coronary tree from monoplane temporal angiographic clinical sequences.

Experimental assessment of new stent technologies: validation of a comparative paired rabbit iliac artery study model.

Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 +/- 4.4% in the right as compared to 9.3 +/- 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 +/- 4.9 mm(3) in the right and 25.8 +/- 3.5 mm(3) in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 +/- 17 mm(2) in the right and 0.76 +/- 0.17 mm(2) in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed.