[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.

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.

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.

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.

Osteoprotegerin, a new actor in vasculogenesis, stimulates endothelial colony-forming cells properties.

BACKGROUND: Osteoprotegerin (OPG), a soluble receptor of the tumour necrosis factor family, and its ligand, the receptor activator of nuclear factor-κB ligand (RANKL), are emerging as important regulators of vascular pathophysiology. OBJECTIVES: We evaluated their effects on vasculogenesis induced by endothelial colony-forming cells (ECFC) and on neovessel formation in vivo. METHODS: Effects of OPG and RANKL on in vitro angiogenesis were evaluated after ECFC incubation with OPG or RANKL (0-50 ng mL(-1)). Effects on microvessel formation were evaluated with an in vivo murin Matrigel plug assay. Vascularization was evaluated by measuring plug hemoglobin and vascular endothelial growth factor (VEGF)-R2 content 14 days after implantation. RESULTS: We found that ECFC expressed OPG and RANK but not RANKL mRNA. Treatment of ECFC with VEGF or stromal cell-derived factor-1 (SDF-1) upregulated OPG mRNA expression. OPG stimulated ECFC migration (P < 0.05), chemotaxis (P < 0.05) and vascular cord formation on Matrigel(®) (P < 0.01). These effects were correlated with SDF-1 mRNA overexpression, which was 30-fold higher after 4 h of OPG stimulation (P < 0.01). OPG-mediated angiogenesis involved the MAPK signaling pathway as well as Akt or mTOR cascades. RANKL also showed pro-vasculogenic effects in vitro. OPG combined with FGF-2 promoted neovessel formation in vivo, whereas RANKL had no effect. CONCLUSIONS: OPG induces ECFC activation and is a positive regulator of microvessel formation in vivo. Our results suggest that the OPG/RANK/RANKL axis may be involved in vasculogenesis and strongly support a modulatory role in tissue revascularization.

[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.

[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.

[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.

[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.

[Sudden death by coronary spasm: a particular and often unrecognised clinical entity]. / Mort subite par s pasme coronaire: une entité particulière, trop souvent méconnue.

The authors report 3 cases of resuscitated sudden death in which the investigations clearly showed coronary spasm. This was demonstrated by systematic coronary angiography with an ergometric test. Two patients underwent electrophysiological investigations which were normal. The three patients were prescribed long-term calcium antagonist therapy and one of them underwent coronary angioplasty. With a follow-up of 6 months to 3 years, there was no clinical recurrence or documented arrhythmia. A review of the literature shows that this is a cause of sudden death which is probably underestimated and unrecognised. Electrophysiological investigations often give disappointing results and medical therapy is the keystone of treatment. Coronary angioplasty and implantation of an automatic defibrillator are second-line treatments reserved to forms refractory to medical therapy.

[Exertional hypertension and sport]. / Hypertension artérielle d'effort et sport.

Defining the normal range of blood pressure during exertion is not easy. Each type of exercise induces increased blood pressure that responds to a particular curve, and adaptation modes differ according to age, gender, physical condition, basal blood pressure, etc. The best studied is blood pressure measured on the arm using a cycloergometre. Classical publications established blood pressure curves according to heart rate during exercise. It appears that the best scale of reference for power developed occurs in individuals who can provide a very high degree of effort and in particular, athletes who are in very good training. According to some authors, hypertension on exertion would entail a poor prognosis, even in the absence of resting hypertension. Nevertheless, there is presently no well established therapeutic recommendation concerning exertion hypertension. This approach could depend on resting blood pressure and on the existence of other risk factors. For an athlete, pursuing physical activity is most often encouraged, sometimes after treatment or adjustment of its level.

[Ventricular arrhythmia in the athlete: practical management]. / Arythmie ventriculaire chez le sportif: conduite pratique.

The aim of athletic competition is to exceed ones present limits, which exposes the athlete to increased risk is helshe has a cardiac disorder. Ventricular excitability is not part of the athletic heart syndrome, and only the presence of resting ventricular extrasystoles that are monomorphic, ungrouped and disappear with exercise can be considered physiological. Significant ventricular arrhythmia can reflect a cardiac disorder that should be routinely sought in order to determine if there is a potential risk of sudden death favoured by physical effort. The confirmation of arrhythmia and seeking a cardiac disorder require a rigorous approach based on history-taking, clinical examination and initial performance of non-invasive, orienting examinations. Invasive examinations, based on the case, are often required if a disorder is suspected or if there is a question concerning the severity of the arrhythmia. Decisions concerning aptitude for competition are decided case by case, according to the disorder, with reference to the 26th Bethesda Conference. If the ventricular arrhythmia is shown to be benign and no underlying cardiac disorder exists, athletic competition may be pursued without restrictions. In case of contrary findings, physical activity will be limited and the authorized level will be precisely determined according to the context and the results of exertion tests made during treatment.

[Hypertrophic cardiomyopathy and sports activities]. / Cardiomyopathie hypertrophique et activités sportives.

What advice should be given today to a patient with hypertrophic cardiomyopathy who wishes to participate in sports? The Bethesda recommendations of 1994 strictly contraindicate competition in sports for any subject with hypertrophic cardiomyopathy, outside of a few activities with a very low level of energy expenditure. Nothing today suggests a change in these recommendations. Even if genetic knowledge of hypertrophic cardiomyopathy has progressed considerably, it is still not possible to determine precisely which forms are specific to a risk of sudden death linked to effort. Some forms of hypertrophic cardiomyopathy can be classified as high risk based on history-taking (familial antecedents of sudden death, syncope) and/or on genetic study, and/or on the results of complementary examinations (lack of blood pressure adaptation on exertion test, ventricular rhythm disorders, etc.) and in such cases extreme prudence should be recommended with regard to physical activity. On the other hand, if results indicate that the patient is at low risk, limited, submaximal physical activity can be envisioned, taking into account the results of the exertion test and Holter readings made during physical activity. Periodic re-evaluation of tolerance to exertion is then indispensable.

[A new case of pericardial thymic cyst]. / Un nouveau cas de kyste thymique paracardiaque.

The thymic cysts are benign tumours of the thymo-pharyngeal canal, usually located in the cervico-mediastinal region. The authors report the case of a large thymic cyst with an ectopic right paracardiac location compressing the right heart chambers. It was a chance finding on chest X-ray of an asymptomatic 21 year old man. Though suggestive of a pericardial cyst in view of its position, curative surgical ablation allowed confirmation of the diagnosis at anatomo-pathological examination.

[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.