The CYP2C19*2 genetic variant is known to contribute to low responsiveness to clopidogrel treatment, leading to a higher rate of cardiovascular events. Systematic identification of the 2C19*2 carriers to predict the individual patient's response to clopidogrel is a matter of debate. Data of the VASP-02 study comparing patients’ responsiveness to 75 and 150 mg/day maintenance dose of clopidogrel (Aleil et al., J Am Coll Cardiol Intv 2008) were reanalyzed by determining the 2C19*2 carrier status of the patients. Platelet reactivity index (PRI) was determined using the VASP method. A PRI>69% defines low responsiveness to clopidogrel. In the 37 non responder patients, 42.4% were 2C19*2 carriers versus 22.0% in the responder patients (p=0.022). After multivariate analysis, 2C19*2 polymorphism and high body weight were two independent predictors of high PRI (odds ratio [95% confidence interval] 3.39 [1.06-10.84] p=0.039 and 3.14 [1.19-8.30] p=0.021) respectively. Increasing the maintenance dose of clopidogrel from 75 to 150 mg/day in non responder patients resulted in a significant decrease of PRI from 76.4±4.6 to 62.8±10.4% (p<0.01) in 2C19*2 carriers and from 76.1±5.3 to 60.8±13.4% (p<0.01) in non carriers. The mean decrease of PRI after doubling the dose was not significantly different between carriers and non carriers of the genetic variant (−13.6±9.3 and −15.3±11.8% p=0.39, respectively). CYP2C19*2 is an important determinant of the responsiveness to clopidogrel while other independent factors such as body weight also are involved. Hyporesponsiveness in 2C19*2 carriers can be easily overcome by doubling the maintenance dose of clopidogrel. Thus, combined functional pharmacodynamic monitoring and genetic determination of CYP profile should help improve patient's responsiveness to clopidogrel.

We investigated whether maintenance therapy with clopidogrel 150 mg/day produces higher platelet inhibition than the standard 75 mg/day dose, and whether the higher maintenance dose increases plate...

Objectives We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day.Background Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel. Methods One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >= 69%). All patients received aspirin 75 mg/day.Results After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group.Conclusions In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40). (J Am Coll Cardiol Intv 2008;1:631-8) (C) 2008 by the American College of Cardiology Foundation

Le stent actif est une nouvelle technologie capable de prévenir le développement de l’hyperplasie intimale et de la resténose dans les suites d’une angioplastie coronaire. Cet article passe en revue ses indications actuelles et ses futures utilisations, à la vue des résultats des principales études et séries publiées.

Drug eluting stent is a new technology aimed to prevent the development of neointimal hyperplasia and restenosis following percutaneous coronary intervention. This review describes the direction for their use at the present time and the future of their utilization with the summary of the principals clinicals trials.

Previous small clinical trials have suggested that treatment with nitric oxide donors in suspected myocardial infarction can reduce mortality by 30-35%. To confirm this finding in a large-scale trial, we compared molsidomine and its active metabolite linsidomine (a nitric oxide donor) with placebo in 4017 patients with acute myocardial infarction.In our trial, patients without signs of overt heart failure (Killip III/lV) were randomly assigned in a double-blind design within 24 h of symptom onset to receive linsidomine 1 mg/h intravenously for 48 h, followed by 16 mg molsidomine by mouth daily for 12 days (n = 2007), or an identical placebo (n = 2010). All other treatments could be used at the responsible physician's discretion with the exception of systematic vasodilator treatment. The molsidomine and placebo groups showed similar all-cause 35-day mortality (168 [8.4%] vs 176 [8.8%] deaths, p = 0.66), and adjustment for baseline variables in a Cox model had no effect. Similarly, we found no difference for long-term mortality(mean follow-up 13 months; 294 [14.7%] vs 285 [14.2%] deaths, p = 0.67). The two groups showed similar frequencies of major and minor adverse events; only headache was significantly more common in the molsidomine group.Changes in treatment practices and the lower risk profile of our study subjects than of participants in previous trials may explain the results. It is still not clear whether nitric oxide donors can improve survival in higher-risk myocardial infarction patients.

One hundred and twenty-seven patients admitted for dizziness, syncope, or a fall were studied prospectively over a six-month period. History taking, a thorough physical evaluation, routine blood tests, a carboxy-hemoglobin serum assay and an ECG with carotid sinus compression were carried out as the initial workup. Additional investigations were then performed as indicated. Most patients were females above 65 years of age. A cause was identified in 87 % of cases. Cardiovascular disease was the leading cause (50 %), followed by neurologic disease, falls due to clumsiness, and abuse of alcohol. The initial workup ensured the diagnosis in 79 % of cases ; more sophisticated investigations provided decisive information in only 10 % of patients. Clinical findings were found to have the greatest diagnostic value (66 %). Among sophisticated investigations, continuous ECG monitoring was most informative (25 %), whereas investigations of the brain were less likely to be helpful. In half the cases, the hospital stay was extended to adjust previous therapy or investigate a disease state discovered during the current hospitalization. These data show that inhospital evaluation, even of short duration, is beneficial in patients with dizziness, syncope or a fall.

Spontaneous idiopathic pneumopericardium (SIPP) in young subjects is a rare disorder since, apart from the case described here, only 28 cases have been reported in the literature. It occurs mainly in young adults. The physiopathology of the disorder involves alveolar rupture, as described by Macklin. The symptoms of SIPP are dominated by chest pain, which usually develops suddenly and is combined with dyspnea. Clinical examination is not very helpful, cardiac auscultation detects either pericardial rubbing or a more suggestive metallic sound. Recovery usually occurs without treatment, but there is a risk of long-term recurrence. An unusual complication to be feared is aerial tamponade, which may be life-threatening and calls for emergency draining. The treatment of SIPP involves strict bed-rest, symptomatic treatment of the pain and clinical monitoring.

Spontaneous idiopathic pneumopericardium (SIPP) in young subjects is a rare disorder since, apart from the case described here, only 28 cases have been reported in the literature. It occurs mainly in young adults. The physiopathology of the disorder involves alveolar rupture, as described by Macklin. The symptoms of SIPP are dominated by chest pain, which usually develops suddenly and is combined with dyspnea. Clinical examination is not very helpful, cardiac auscultation detects either pericardiac rubbing or a more suggestive metallic sound. Recovery usually occurs without treatment, but there is a risk of long-term recurrence. An unusual complication to be feared is aerial tamponade, which may be life-threatening and calls for emergency draining. The treatment of SIPP involves strict bed-rest, symptomatic treatment of the pain and clinical monitoring.

Pneumopericardium is defined as the presence of air in the pericardial cavity. It is a rare condition in adults, usually due to trauma; it is commoner in the more exposed neonate and usually iatrogenic. The clinical presentation of chest pain and shortness of breath is associated with the pathognomonic auscultatory sign described by Bricheteau: a water-mill bruit. The diagnosis is confirmed by chest X-ray which shows the air-gap sign surrounding the cardiac silhouette. The principal differential diagnosis is a pneumomediastinum. The prognosis of pneumopericardium depends on the cause and complications of which tamponade and infection are the most serious and potentially life-threatening. The treatment of pneumopericardium is bed rest and surveillance when uncomplicated: evacuation of the air becomes necessary when complications set in.

C'est une pathologie rare chez l'adulte, habituellement d'origine traumatique, plus frequente chez le nouveau-ne fragilise, et d'origine iatrogene. La symptomatologie clinique est dominee par la douleur thoracique et la dyspnee, associees au signe pathognomonique auscultatoire decrit par Bricheteau: le bruit de moulin. Le diagnostic de certitude est effectue par la radiographie de face revelant une bande hyperclaire (l'air) entourant le cœur, elle-meme cernee par un lisere radio-opaque (le pericarde). Le pronostic de pneumopericarde depend de sa cause et de ses complications: la tamponnade, et l'infection. Le traitement est lie a la survenue des complications, repos et surveillance si elles sont absentes, drainage de l'epanchement aerique si elles surviennent

Pneumopericardium is defined as the presence of air in the pericardial cavity. It is a rare condition in adults, usually due to trauma; it is commoner in the more exposed neonate and usually iatrogenic.The clinical presentation of chest pain and shortness of breath is associated with the pathognomonic auscultatory sign described by Bricheteau: a water-mill bruit.The diagnosis is confirmed by chest X-ray which shows the airgap sign surrounding the cardiac silhouette.The principal differential diagnosis is a pneumomediastinum.The prognosis of pneumopericardium depends on the cause and complications of which tamponade and infection are the most serious and potentially life-threatening.The treatment of pneumopericardium is bed rest and surveillance when uncomplicated: evacuation of the air becomes necessary when complications set in.

127 patients were admitted to medical units because of malaises, syncopes and falls. The causes were found in 87% of the patients, mainly cardiovascular. In 50% of the patients, admission resulted in adjustment of treatment or finding and other pathology.

Amiodarone modifies thyroid hormone secretion and hypothyroidism occurs in some cases. The latter diagnosis is often difficult and is of particular importance in these patients as it may have serious consequences for the heart. Early diagnosis is therefore essential but difficult because of the induced hyperthyroxinemia with maintenance of euthyroidism and a hypotriiodothyronemia. The diagnostic performance of an ultrasensitive method of measuring TSH (TSH-U), capable of distinguishing hyper and euthyroidism were compared with standard thyroid function tests and TSH stimulation with TRH in 50 patients treated with amiodarone. Only 6 of the 14 patients with hyperthyroxinaemia had TSH-U values in the hyperthyroid range: only one of these patients had an increased triiodothyronine. In 2 cases the THS-U was low but the T4L was normal. In 4 patients, increased TSH-U allowed diagnosis of latent or patent hypothyroidism. There was a close correlation between results of the TRH stimulation test and those of the TSH-U in all cases. This test may therefore be used as an initial screening test for thyroid dysfunction in patients on amiodarone and is simple, reliable and relatively cheap to perform. It makes it unnecessary to measure all thyroid hormonal parameters and the TRH test simultaneously.