Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions: Prevalence and Role of Osteoprotegerin and Pericytes.

OBJECTIVE/BACKGROUND: Arterial calcification, a process that mimics bone formation, is an independent risk factor of cardiovascular morbidity and mortality, and has a significant impact on surgical and endovascular procedures and outcomes. Research efforts have focused mainly on the coronary arteries, while data regarding the femoral territory remain scarce. METHODS: Femoral endarterectomy specimens, clinical data, and plasma from a cohort of patients were collected prospectively. Histological analysis was performed to characterize the cellular populations present in the atherosclerotic lesions, and that were potentially involved in the formation of bone like arterial calcification known as osteoid metaplasia (OM). Enzyme linked immunosorbent assays and cell culture assays were conducted in order to understand the cellular and molecular mechanisms underlying the formation of OM in the lesions. RESULTS: Twenty-eight of the 43 femoral plaques (65%) displayed OM. OM included osteoblast and osteoclast like cells, but very few of the latter exhibited the functional ability to resorb mineral tissue. As in bone, osteoprotegerin (OPG) was significantly associated with the presence of OM (p = .04). Likewise, a high plasma OPG/receptor activator for the nuclear factor kappa B ligand (RANKL) ratio was significantly associated with the presence of OM (p = .03). At the cellular level, there was a greater presence of pericytes in OM+ compared with OM- lesions (5.59 ± 1.09 vs. 2.42 ± 0.58, percentage of area staining [region of interest]; p = .04); in vitro, pericytes were able to inhibit the osteoblastic differentiation of human mesenchymal stem cells, suggesting that they are involved in regulating arterial calcification. CONCLUSION: These results suggest that bone like arterial calcification (OM) is highly prevalent at femoral level. Pericyte cells and the OPG/RANK/RANKL triad seem to be critical to the formation of this ectopic osteoid tissue and represent interesting potential therapeutic targets to reduce the clinical impact of arterial calcification.

Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients.

OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1ß. Wild-type, jnk1(-/-)-jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1ß stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1ß, may contribute to inflammation and bone erosions in RA.

[Advocate for a secondary prevention assessment of coronary artery disease]. / Plaidoyer pour un bilan de prévention secondaire de la coronaropathie.

Secondary prevention is paramount in patients who are survivors of an acute coronary syndrome. Cardiac rehabilitation has proven to be effective for several decades in the long-term implementation of preventive measures. Despite this evidence, prescription and real participation in these programs remain limited for a many reasons, including the patient, physician, health care system. Recent statistics are a major regional disparity in prescription that leads to inequality in access to care. A reflection is therefore necessary on the organization of the course of care of the patient after an acute coronary syndrome. The secondary prevention plan that we are proposing here is based on a secondary prevention assessment that allows the patient to be guided in rehabilitation or in an alternative proposal.

[Normal values of the peak early diastolic Ea using myocardial tissue Doppler in 100 elite athletes]. / Valeur normale du pic protodiastolique Ea au doppler tissulaire myocardique chez les athlètes de haut niveau, à propos de cent sportifs.

INTRODUCTION: Intense physical training can induce morphological and functional changes in the heart, leading to 'Athlete's heart'. This can be responsible for adaptive left ventricular hypertrophy (LVH), which is sometimes difficult to differentiate from hypertrophic cardiomyopathy (HCM) with its inherent threat to life. Echocardiography usually allows the diagnosis to be clarified, but in borderline cases it can be insufficient. OBJECTIVE: The value of myocardial tissue Doppler (MTD) in the diagnosis of HCM has been highlighted recently. Normal values in athletes have been published, but these series have only studied a small number of athletes in a small number of sporting disciplines. METHODS: Using echocardiography with MTD at the lateral mitral annulus, we therefore evaluated 100 elite athletes from a very wide range of disciplines, in order to obtain a mean reference value for early diastolic Ea velocities. RESULTS: The peak early diastolic Ea was measured at 18.2 +/- 2.7 cm/s. The E/A ratio was 1.7 +/- 0.4. We found that 75% of the athletes had a value for Ea=17 cm/s, and for 84% of them the E/Ea ratio was correlated positively with the E/A ratio, and negatively with age. CONCLUSION: Elite athletes have early diastolic velocities measured with MTD that are higher due to their physical training. This study has allowed a mean reference value to be established for Ea in this specific population, with the potential opportunity to distinguish between LVH and HCM.

[The best of cardiac rehabilitation in 2006]. / L'essentiel de l'année 2006 en réadaptation cardiaque et cardiologie du sport.

The meta-analysis showing the benefits of physical training revisited: Taylor examined only the cardiac rehabilitation trials of exercise intervention alone (versus usual care) and demonstrated that cardiac mortality is 28 % reduced and exercise appears to have an independent mortality benefit. An economic evaluation of cardiac rehabilitation: a systematic review of 15 economic evaluations. Evidence to support the cost-effectiveness of supervised cardiac rehabilitation compared with usual care in myocardial infarction and heart failure was identified. But further well-designed trials are required. Pronostic value of some variables determined by exercise testing entering cardiac rehabilitation and after physical training. A beneficial effect of physical training versus usual care on BNP and neurohormones in patients with chronic heart disease. Patients on beta blockers after myocardial infarction: determination of a more accurate training heart frequency derived from the classical Karvonen's formula. The combination of trimetazidine with exercise training provides greater improvements in functional capacity, left ventricular function and the endothelium-dependent relaxation of the brachial artery than exercise training alone in patients with ischaemic cardiomyopathy referred for cardiac rehabilitation. Guidelines for resistance exercise after cardiac event: a new paradigm less restrictive, safe and efficient to accelerate patients' return to daily activities. Recommendations for participation in leisure-time physical activity and competitive sports for patients with ischaemic heart disease: the result of consensus among experts from the ESC study group of sports cardiology.

[Specific features of the interrogation and examination of athletes]. / Particularités de l'interrogatoire et de l'examen clinique du sportif.

The motivations of a physician and a competitive athlete are fundamentally divergent. A competitor has short-term objectives and wants to win whatever the cost physically and to obtain the attention of the media. The physician's priorities are a healthy and long life for his patient and therefore looks to the future with precautionary measures. Medical confidentiality is a fundamental ethic of the profession (which does not help the sporting journalists...). The physician who chooses to look after top class athletes should not lower his ethical principles but should absolutely understand the motivations of competitors.

[The heart and the mountains]. / Coeur et montagne.

In a normal subject, exposure to high altitude is accompanied by a diminution in performance that is proportional to the hypoxia. In order to advise a cardiac patient who is contemplating undertaking a physical activity in the mountains and wishes to avoid taking any unnecessary risks in an environment that can quickly become very hostile, it is important to have a recent evaluation of the cardiopathy, and some appreciation of the expected problems linked to the activity and the location. Certain pathologies are absolute contraindications to high altitude, such as pulmonary arterial hypertension, thrombo-embolic disease, and unstable cardiac disease. The majority of stable cardiopathies allow some modified activity. The role of the cardiologist is to evaluate the patient's functional capacity, to calculate the effect of altitude on this capacity, and to postulate whether the reserve will be sufficient to cope with the expected demand.

[Screening for high risk cardiac diseases in athletes]. / Le dépistage des cardiopathies a risque chez le sportif.

The prevention of cardiovascular complications occurring during sporting activity requires detection of well-known pathologies which are often clinically latent but which may present with sudden death. The problem of detection and the recommendations and French laws concerning this subject are summarised in this article.

[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.

Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model.

Receptor activator of nuclear factor kappa-B (RANK) and RANK-ligand are relevant targets for the treatment of polyethylene particle-induced osteolysis. This study assessed the local administration of siRNA, targeting both human RANK and mouse Rank transcripts in a mouse model. Four groups of mice were implanted with polyethylene (PE) particles in the calvaria and treated locally with 2.5, 5 and 10 µg of RANK siRNA or a control siRNA delivered by the cationic liposome DMAPAP/DOPE. The tissues were harvested at day 9 after surgery and evaluated by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) immunohistochemistry for macrophages and osteoblasts, and gene relative expression of inflammatory and osteolytic markers. 10 µg of RANK siRNA exerted a protective effect against PE particle-induced osteolysis, decreasing the bone loss and the osteoclastogenesis, demonstrated by the significant increase in the bone volume (P<0.001) and by the reduction in both the number of TRAP(+) cells and osteoclast activity (P<0.01). A bone anabolic effect demonstrated by the formation of new trabecular bone was confirmed by the increased immunopositive staining for osteoblast-specific proteins. In addition, 5 and 10 µg of RANK siRNA downregulated the expression of pro-inflammatory cytokines (P<0.01) without depletion of macrophages. Our findings show that RANK siRNA delivered locally by a synthetic vector may be an effective approach for reducing osteolysis and may even stimulate bone formation in aseptic loosening of prosthetic implants.

Assessment of left ventricular stiffness and compliance.

Invasive and non-invasive methods exist to assess left ventricular compliance (LVC). This work has two parts, one experimental and one clinical. We estimated left chamber stiffness in dogs by using volume data from radionuclide ventriculography (RNV) and left ventricular pressure data, synchronized with a gating system to the intraventricular dp/dt max to obtain volume and pressure data from a mean cardiac cycle. In five dogs after acute experimental ischaemia, the modulus chamber stiffness Kp rose from 30.2 +/- 4.4 to 55.4 +/- 5.9 (P < 0.01). In 10 dogs with experimental infarction after intra-aortic balloon pumping, Kp decreased from 33.7 +/- 5.0 to 15.5 +/- 3.9 (P < 0.01) and in five dogs with experimental infarction, after intravenous infusion of sodium nitroprusside, Kp decreased from 41.4 +/- 5.5 to 22.2 +/- 2.8 (P < 0.01). In eight normal volunteers and in 20 postmyocardial infarction patients, we estimated a parameter reflecting the LVC by using volume data with blood flow velocity at the mitral valve annulus. Assuming that the mitral flow-velocity variation reflects LV pressure changes, the formula LVC = (dv/dt)/(dp-dt) becomes (dv/dt)/(df/dt) = dv/df. Values obtained in normals were 0.841 +/- 0.295 m-1s and after myocardial infarction 0.331 +/- 0.10 m-1s. Both methods allow clear separation in groups of animals or patients according to the expected changes in LVC or stiffness.

[Mitral flow during exercise in the healthy young adult. Use of an ultrasonic probe device]. / Etude du flux mitral pendant l'effort chez l'adulte jeune sain. Utilisation d'un porte-sonde.

Mitral flow velocity was studied during upright exercise on a bicycle ergometer using an original ultrasonic probe support device capable of maintaining a stable apical 4-chamber position. The Doppler sample volume was positioned at the tips of the mitral leaflets. Twelve men (mean age 25.3 +/- 5.8 years) without cardiac disease were studied. Exercise stress testing was performed with 30 watt increments of load of 3 minutes duration up to 120 watts. Mitral flow was recorded before exercise and at each increment of load until the exercise led to an average heart rate increase of 94%. The following changes were observed during exercise: a reduction in the duration of mitral flow (duration MF) and of the Duration MF/RR ratio; an increase in the mean mitral flow velocity of 154% at peak effort compared with basal values and the maximum A and E wave velocities which increased from T0 to T6 from 47 +/- 8.9 to 76 +/- 13 cm/s and from 62.4 +/- 13.1 to 107.8 +/- 14.9 cm/s respectively; the A/E ratio remained stable; mitral velocity time integrals (VTI) remained stable, indicating an increase in mitral surface area during exercise; the stability of the VTI at the A and E waves in absolute values but a mild increase of the A wave VTI/mitral VTI ratio, suggesting a slight increase in the role of atrial contraction during exercise. These results show that the increase in mitral flow velocity during upright exercise on a bicycle ergometer in healthy young adults is accompanied by a constant A/E ratio and mitral VTI which indicates that the mitral surface area increases on effort.

[Determination of variability factors of arterial pressure using 3843 self-measurements of blood pressure in 34 active hypertensives]. / Approche des facteurs de variabilité de la pression artérielle par 3 843 automesures tensionnelles chez 34 hypertendus actifs.

To assess the role of physical activity, stress and treatment on BP variations in working hypertensives we used repeated self measurements of BP which are cheaper and more simple than ambulatory BP measurements but allow for a smaller number of measurements. 34 working hypertensives self measured daily life BP, at home and at workplace, 7 times a day, for at least one week, before and 6 weeks after beta-blockade with metoprolol 200 to 400 mg daily. They used a Spengler SP9 electronic sphygmometer and specified on 4 grades scales their physical activity and stress just before measurement. The time for self measurement of BP was settled according to occupations more than to clocktime. The equipment was standardized at each visit by measuring BP with a mercury manometer then with the electronic sphygmometer. There were no significant differences neither for SBP nor for DBP and the two measures correlate closely (r = 0.91), P = 0.0001). Analysis of variance on SBP exhibits the role of time (p (0.001) and stress (p (0.0001). Physical activity does not interfere (p = 0.19). There is no difference between work days and sundays (p = 0.17). Treatment effect was very strong (p (0.0001) but there was no interaction neither with physical activity nor stress. Analysis of variance on DBP exhibits similar results except that BP on workdays is significantly higher than on sundays (p = 0.03). We conclude that: Repeated self measurement of BP is able to display variation of BP with occupations and stress. Beta-blockade lowers BP but does not interfere with variability.

[Exercise echocardiography and study of the left ventricle in sportsmen during exertion]. / Echocardiographie d'effort et étude du ventricule gauche des sportifs pendant l'effort.

The use of an original ultrasonic transducer holder has made possible the recording of M mode and 2D echocardiography during exercise. Left ventricular function was studied during upright bicycle exercise in two groups: 10 trained athletes (Group A) and 10 normal subjects (Group B). All were 20 years of age. Satisfactory echocardiograms were obtained up to a mean heart rate of 180/mn which corresponded to an average work load of 180 W in Group B and 300 W in Group A. The cardiac output was comparable in the two groups up to a 180 W load, but in Group A a lower HR was compensated by a larger stroke volume (SV). The increase in SV in Group A was related to a greater LV end-diastolic dimension (LVEDD) during exercise, whereas the ejection fraction increased less than in the control group. During very strenuous exercise (Group A only) further increases in cardiac output were related mainly to an increased heart rate and to a lesser degree to increased LVEDD and ejection fraction.

[Effects of different types of continuous emission laser on human atheromatous plaques in vitro]. / Effets de différents types de lasers à émission continue sur les plaques athéromateuses humaines in vitro.

The laser beam is a punctual source of thermal energy which can be used to vaporize human atheroma. The physical characteristics of optimal utilisation (total energy, wave length, continuous or pulsed emission) have not been clearly defined. We carried out in vitro irradiations of human atheromatous material and healthy arterial wall with different combinations of power-emission time and three different wave lengths, using four continuous emission laser beams (Nd-Yag, two CO2 with different lenses, Argon). The beam emitted by the Nd-Yag was absorbed less than the CO2 and Argon lasers, which had comparable effects above a threshold of 2 to 14 joules. The weight of vaporized fibro-atheromatous material was 0.11 mg per joule of optical energy dissipated (CO2). No radical difference was observed in the nature of the effects of the three types of laser studied. The problems of using this technique on the beating heart remain unsolved (ballistics of the emerging ray). Other modes of emission (pulsed) and different wave lengths should be studied.

[Quantitative study of the pulmonary uptake of thallium 201 during exercise and redistribution in the coronary patient]. / Etude quantitative de la fixation pulmonaire du thallium 201 à l'effort et lors de la redistribution chez l'insuffisant coronaire.

In some patients with coronary disease hyperactivity of the lungs is commonly observed when the myocardial scintigraphic images are recorded during exercise. Pulmonary activity of radionuclide tracers has been reported in the literature and quantified in different ways. The present study contributes to this quantification by suggesting a new index: the pulmonary activity to cardiac activity percentages ratio during exercise and blood redistribution. The value of the new index has been evaluated comparatively in 11 subjects with normal coronary arteries (0.76 +/- 0.09) and in 39 patients with angiographically proven coronary disease (0.92 +/- 0.10; p less than 0.001). Remarkably, this index hardly varies in normal subjects and therefore is a highly specific aid to diagnosis. In coronary patients, multivariate analysis has shown that it correlates in decreasing order of intensity with: (1) a left ventricular end-diastolic pressure of 14 mmHg or more; (2) a moderate rise in heart rate at exercise; (3) a moderate heart work; (4) an ST depression of 2 mm or more; (5) a multilocular myocardial ischaemia at scintigraphy. Our index did not prove capable of discriminating between one-, two- or three- vessel diseases. In view of the data obtained in this study and those found in the literature, this index should be regarded as a reliable marker of left ventricular dysfunction during stress. Being relatively inexpensive and easy to obtain, it complements myocardial scintigraphy and may be useful in clinical practice.

[Myocardial infarction and anabolic steroid use. A case report]. / Infarctus du myocarde et prise d'anabolisants. A propos d'un cas.

The potential cardiotoxicity of anabolic steroids is not well known. The authors report the case of a young man who was a top class body builder and who developed severe ischaemic cardiomyopathy presenting with an inferior wall myocardial infarction. The clinical history revealed prolonged and intensive usage of two types of anabolic steroids to be the only risk factor. This cardiotoxicity may be related to several physiopathological mechanisms: accelerated atherogenesis by lipid changes, increased platelet aggregation, coronary spasm or a direct toxic effect on the myocytes. The apparent scarcity of the reported clinical details in the literature is probably an underestimation of the consequences of this usage.

[Postpericardiotomy syndrome; a rare complication of transcavitary cardiac pacing: apropos of a case]. / Syndrome pleuro-péricardique; une complication rare de la stimulation cardiaque par voie endocavitaire. A propos d'un cas.

The authors report a new case of the post-pericardiotomy syndrome occurring after implantation of a DDD pacemaker. This is a rare complication of the insertion of a screw atrial electrode, the iatrogenic potential of which has already been reported. The immediate outcome was favourable with anti-inflammatory therapy.

[Chronic occlusion of the left coronary artery]. / Occlusion chronique du tronc coronaire gauche.

Chronic occlusion of the left main coronary artery is rare with less than 100 reported cases. the treatment is essentially surgical but medical management has been proposed. This case report illustrates the prognostic benefit of surgical management in view of the risk of secondary occlusion of the proximal right coronary artery.

[Traumatic tricuspid insufficiency. 5 cases]. / L'insuffisance tricuspide traumatique. 5 observations.

Five men (mean age 39 years) were followed up for 6 to 60 months for tricuspid valve regurgitation caused by a front-to-back injury (in a car in four cases, in an aircraft in one case). The time elapsed between the accident and the signal symptoms varied from 28 days to 20 years. The condition was diagnosed on clinical data (stage 2) and on the results of echocardiography and cardiac catheterization. Four patients were operated upon and provided with a bioprosthetic valve. The post-operative period was marked by resolutive atrioventricular block in one case and inferior myocardial infarction in one case. Four points ought to be highlighted: 1. The long-term development of dilatation of the annulus, cicatricial fibrosis or altered left ventricular contractility; 2. The usefulness of pulsed Doppler echocardiography for the diagnosis and surgical indications (quantification of the regurgitation, right ventricular kinetics); 3. The adaptation of treatment to the lesion: repair whenever possible, or annuloplasty, or bioprosthetic valve replacement (mechanical valves must be excluded); 4. The time for surgery is difficult to determine in view of the asymptomatic period, which may be very long. The decision to operate is based on clinical, echocardiographic, haemodynamic and dromotropic (complete arrhythmia due to atrial fibrillation) data. This decision must be reached before right ventricular myocardial deterioration sets in.