[Anomalous origin of right coronary artery from pulmonary artery associated to left main coronary stenosis]. / Anomalie de connexion de l'artère coronaire droite au niveau de l'artère pulmonaire associée à une sténose du tronc commun gauche.

We describe herein a case of a 16 years-old female patient referred to our department for further exploration of a chest pain. Color Doppler echocardiography revealed an abnormal flow at the level of the pulmonary artery. Exercise testing was abnormal leading to further imaging including computed cardiac tomography followed by coronary angiography which showed anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) associated with mid shaft left main stenosis. We discuss this uncommon association and therapeutic options.

Covid-19 et système cardiovasculaire / Covid-19 and cardiovascular system

L'expansion planétaire du covid19 représente une crise sans précèdent ; cette pandémie a fait plus d'un million de mort en une année. En plus de l'atteinte pulmonaire, le virus a des implications majeures sur le système cardiovasculaire : les maladies cardiovasculaires pré existantes représentent un facteur de risque d'infection sévère avec augmentation de la mortalité, d'autre part l'infection entraine des complications cardiovasculaires qui aggravent le pronostic. Le lien entre le Covid19 et le système cardiovasculaire découle principalement de la voie d'entrée cellulaire du virus qui est assurée par sa liaison à une protéine membranaire l'enzyme de conversion de l'angiotensine (ECA), qui joue un rôle clé dans la régulation neurohumorale ; cette protéine est très présente au niveau du cœur et du poumon, d'où le tropisme du virus qui entraine la dysrégulation de cette voie cellulaire avec des répercussion sur la fonction cardiaque et respiratoire. Une polémique a déferlé concernant les traitements anti hypertenseurs et notamment les inhibiteurs du système rénine angiotensine aldostérone mais après évaluation des données actuelles, il est de consensus de ne pas arrêter ou changer les traitements anti hypertenseurs. L'augmentation des troponines cardiaques est un facteur de mauvais pronostic qui aggrave le tableau. La myocardite est définie par une inflammation myocardique, Les tableaux cliniques sont variables de la forme légère à la forme grave ; les biomarqueurs myocardiques restent un test incontournable en cas de suspicion clinique, le pronostic est incertain avec des formes fulminantes qui peuvent régresser et enfin pour le traitement les corticoïdes semblent être efficaces. Une autre complication du virus sont les accidents thrombo-emboliques et le dilemme occasionné par le risque accru aux thromboses et la thrombopénie induite par l'utilisation de l'héparine (TIH). On note une augmentation de l'incidence des syndromes coronaires aigus chez les sujets atteints du covid19.

The global expansion of covid19 represents a global crisis; this pandemic killed more than a million people in one year. In addition to pulmonary involvement, the virus has major implications on the cardiovascular system: pre-existing cardiovascular diseases represent a risk factor for severe infection with increased mortality, on the other hand the infection causes cardiovascular complications which worsen the prognosis. The link between the Covid19 and the cardiovascular system stems primarily from the virus's cellular entry pathway, which is provided by its binding to a membrane protein, the angiotensin converting enzyme (ACE) wich plays a key role in neurohumoral regulation; this protein is very present in the heart and lungs, hence the tropism of the virus which causes the dysregulation of this cellular pathway with repercussions on cardiac and respiratory function. A controversy broke out concerning the antihypertensive treatments and in particular the inhibitors of the renin angiotensin aldosterone system but after evaluation of the current data, there is a consensus not to withhold or change the treatments. The increase in cardiac troponins is a factor of poor prognosis which worsens the picture. Myocarditis is defined by myocardial inflammation, its clinical form ranges from the mild form to the severe one; the myocardial biomarkers remain an essential when the clinical suspicion rise, the prognosis is uncertain with fulminant forms which can regress; for treatment corticosteroids seem to be effective. Another complication of the virus are thromboembolic events and the dilemma caused by the increased risk of thrombosis and thrombocytopenia induced by the use of heparin (TIH), and there is an increase in the incidence of acute coronary syndromes in patients affected by covid19.

Assessment for Pulmonary Artery Hypertension Using Clinical and Echocardiographic Criteria in Patients With Systemic Sclerosis.

BACKGROUND: Prognosis of systemic sclerosis (SSc) is affected by pulmonary artery hypertension (PAH). METHODS: Among 202 patients (mean age: 46.1 ± 13.3 years; 177 women) with SSc, those with a tricuspid regurgitation (TR) jet maximal velocity at 2D-echocardiography (2DE) < 2.8m/second were not considered at high risk for PAH, whereas those with a TR velocity >3m/second or between 2.8 and 3m/second and associated with dyspnea were. RESULTS: Among 22 patients at risk, 15 (mean age: 50.4 ± 14.3 years) had definite precapillary PAH on right heart catheterization (RHC). The delay period between recognitions of SSc and PAH was 12.9 ± 5.2 years. Dyspnea was present in all 15 patients, 11 (73.3%) being in the New York Heart Association class III or IV. The 2DE showed normal left ventricular geometrics and function (n = 15), enlargement of the right-sided cardiac chambers (n = 12), increased pulmonary arterial resistances with a TR velocity to pulmonary time-velocity integral ratio of > 0.2 (n = 15) and impaired right ventricle function (n = 15). RHC showed severe PAH in all 15 patients (mean pulmonary artery pressure: 48 ± 17mmHg and mean right atrial pressure: 11.8 ± 4.4mmHg) and a reduced cardiac index (2.2L/m²). There was no statistical difference between patients with and without PAH regarding age, sex ratio, duration from onset of disease, diffuse or cutaneous limited type of SSc, Rodnan severity score and presence of digital ulcerations or autoantibodies. Telangiectasia (P = 0.01) and New York Heart Association class III or IV heart failure (P = 0.001) were more frequent in patients with PAH. CONCLUSION: A combined clinical and Doppler-coupled 2DE screening of PAH risk in patients with SSc is useful to select those who can undergo RHC.

High on treatment platelet reactivity.

The addition of clopidogrel to aspirin for patients undergoing percutaneous coronary intervention (PCI) had significantly reduced cardiovascular events. However, despite dual antiplatelet therapy ischaemic events still occur, especially stent thrombosis, which is associated with a high mortality rate. Inter-individual response to clopidogrel is highly variable. It was shown that 4-46% could be considered as high on treatment platelet reactivity (HTPR). Recent studies had demonstrated a relationship between HTPR and ischaemic events in the setting of PCI. Actually the assessment of platelet reactivity in routine practice and its interpretation to make a decision is a debatable issue.

High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

OBJECTIVES: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. BACKGROUND: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR. METHODS: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. RESULTS: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70). CONCLUSIONS: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.

Level of adenosine diphosphate receptor P2Y12 blockade during percutaneous coronary intervention predicts the extent of endothelial injury, assessed by circulating endothelial cell measurement.

OBJECTIVES: We aimed to investigate whether clopidogrel-induced inhibition of platelet reactivity could reduce the level of circulating endothelial cells (CEC), reflecting the endothelial injury induced by percutaneous coronary intervention (PCI). BACKGROUND: Clopidogrel loading dose before percutaneous coronary angioplasty (PCI) reduces platelet activation through a selective and irreversible blockade of the adenosine diphosphate (ADP) receptor P2Y(12). The impact of clopidogrel on endothelial cells has been scarcely studied. METHODS: A total of 149 patients undergoing PCI for stable angina were enrolled. Levels of CEC were measured at baseline (H0) and 6 (H6) and 24 (H24) h after the procedure using a CD146-based immunomagnetic separation assay. The CEC delta-change (CEC at H6 - CEC at H0) was analyzed according to ADP receptor P2Y(12) blockade, assessed by a vasodilator-stimulated phosphoprotein (VASP) assay after a 600-mg loading dose of clopidogrel. RESULTS: The PCI induced a significant rise in CEC levels 6 h after the procedure. The CEC peak value was significantly higher in patients with high on-treatment platelet reactivity (VASP index ≥50%: 59.6 ± 27.5 cells/ml) as compared with good responders (VASP index <50%: 27 ± 22 cells/ml; p = 0.04). The endothelial injury, assessed by CEC delta-change between H6 and H0, was significantly higher in the high on-treatment platelet reactivity group compared with the good responders group (52.6 ± 25.6 vs. 18.6 ± 23.5, respectively; p < 0.001) and correlated with the VASP index (r = 0.59; p < 0.001). In multivariate analysis, VASP group, the number of diseased vessels, and the number of implanted stents independently predicted the endothelial injury (p < 0.001). CONCLUSIONS: Optimal ADP receptor P2Y(12) blockade reduces the endothelial injury during PCI. This protective effect of clopidogrel on endothelial cells could add to the clinical benefit associated with this drug.

Clopidogrel loading dose adjustment according to platelet reactivity monitoring in patients carrying the 2C19*2 loss of function polymorphism.

OBJECTIVES: We aimed to investigate the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19*2 loss-of-function polymorphism undergoing percutaneous coronary intervention for an acute coronary syndromes. BACKGROUND: CYP2C19*2 polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after percutaneous coronary intervention. METHOD: A prospective multicenter study enrolling 411 patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥ 50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP2C19 was determined by allele-specific polymerase chain reaction. In patients carrying CYP2C19*2 and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 600 mg LDs to obtain a VASP index <50%. RESULTS: One hundred thirty-four patients (35.3%) carried at least one 2C19*2 allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19*2 carriers exhibiting HTPR to reach a VASP index <50%. CONCLUSIONS: Increased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of-function CYP2C19*2 polymorphism.

Early and late outcomes of clopidogrel and coumadin combination for patients on oral anticoagulants undergoing coronary stenting.

BACKGROUND: In patients under oral anticoagulant requiring percutaneous coronary intervention (PCI) with stent implantation, the optimal association between aspirin, clopidogrel and oral anticoagulant (OAC) remains cumberstome. Triple therapy and dual therapy using aspirin and OAC have been evaluated and are associated with a high frequency of major bleedings. The combination of clopidogrel and OAC has never been evaluated. OBJECTIVE: We aimed to investigate the safety and efficacy of clopidogrel and OAC in patients requiring OAC undergoing PCI for acute coronary syndrome. METHODS: A monocenter retrospective study was undertaken between 2000 and 2006 and included all patients undergoing PCI with stent implantation on OAC. On discharge dual therapy with clopidogrel and OAC was prescribed. The primary end-point was the frequency of major TIMI bleedings. Secondary end-points were major cardiovascular event (MACE). Results are reported as rate of events with 95% confidence intervals (CI). RESULTS: Two hundreds and nine patients were followed for 71 +/- 22 months. The indication for oral anticoagulation was atrial fibrillation in 80% of patients, a valvular prothesis in 18% and a history of pulmonary embolism in 5%. The rate (95%CI) of major bleeding was 2.4% (0.9%-5.8%) 2.87% (1.17%-6.44%) and 3.8% (1.79%-7.68%) at 1 month, 12 months and 71 months respectively, which represent 8 events among which 2 were fatal. The MACE rate (95%CI) was low: 0% at one month, 3.8% (1.79%-7.68%) at 12 months and 24.4% (19.07%-30.65%) at 71 months of follow up. Only one stent thrombosis was recorded at the ninth month. The overall rate of death was 9.5% (6.28%-14.32%) among which 2.87% (1.17%-6.44%) were of cardiovascular origin. CONCLUSION: The use of clopidogrel and OAC combination in patients on OAC undergoing coronary stenting is safe and efficient at the short-term. At the long-term, this combination is probably not safe, with a relatively high incidence of fatal stroke.

Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy.

Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 –VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.