Frequency and management of troponin I elevation in patients treated with molecular targeted therapies in phase I trials.

BACKGROUND: Cardiotoxicity of molecular targeted therapies (MTT) is poorly understood and is being investigated among patients with metastatic solid tumours. The frequency of cardiac events among patients receiving MTT has been evaluated in various ways, particularly troponin elevations. PATIENTS AND METHODS: We prospectively evaluated cardiotoxicity among patients included in Phase 1 trials receiving molecular targeted therapies (MTT) for a metastatic solid tumour. At baseline, all patients were examined before the first cycle and monitored including a clinical examination, ECG and troponin I measurement. A trans-thoracic echocardiography was performed at baseline and before each cycle. Patients were enrolled in different trials investigating : an anti-VEGF monoclonal antibody, anti-VEGFR tyrosine kinase inhibitors, and a kinesin inhibitor. RESULTS: Among the 90 patients evaluated, 10 (11%) experienced chest pain and troponin I elevation (n = 2,20%) or asymptomatic troponin I elevation (n = 8, 80%) during follow-up. All patients were re-evaluated at the time of symptoms or troponin I elevation with trans-thoracic echocardiography, cardiac magnetic resonance and coronary angiography. All except one patient, had a normal LVEF during their re-evaluation. One patient exhibited ECG changes (T wave inversion). No QTc interval prolongation was found. On cardiac magnetic resonance, no late gadolinium myocardial enhancement was observed. All coronary angiographies were normal (no occlusion, or coronary stenosis >50%). All patients received beta blockers and aspirin. All Patients were re-challenged with the study drug and no cardiotoxicity was observed during follow up. CONCLUSION: Troponin elevations are frequent among patients receiving molecular targeted therapies. Re-challenging these patients after a careful evaluation and under medical treatment seems to be possible. The mechanism underlying troponin elevations does not seem to be associated with coronary occlusion nor with toxic myocarditis.

Dissection in Marfan syndrome: the importance of the descending aorta.

AIMS: To better characterize patients with Marfan syndrome who have survived an acute aortic dissection and to estimate the risks of events in the descending aorta. Up until now, this portion of the aorta has not been well studied but is gaining importance due to improved patient survival. METHODS AND RESULTS: We report a retrospective cohort of 100 Marfan patients who survived an aortic dissection. Dissection occurred in either the ascending aorta (AscAo) (n = 37), the descending aorta (DescAo) (n = 20), or both (As + DescAo, n = 43). During a mean follow-up of 9.8 ± 6.0 years (complete for 88% of the patients), 17 patients died and 52 had a clinical event (new aortic dissection, surgery, ischaemia, haemorrhage), 60% of which involved the descending aorta. Event-free survival was similar whatever the location of the aortic dissection. However, a better event-free survival was observed when no dissected portion of the aorta remained after surgery, which was the case in 62% (23/37) of the AscAo patients (30% incurred an event vs. 86%; P = 0.008 by log-rank test). Interestingly, the diameter of the ascending aorta was below the surgical threshold in 60% of the patients who incurred a dissection of the descending aorta, and within the normal range in 25%. CONCLUSION: The descending aorta may dissect whatever the diameter of the ascending aorta. The descending aorta is the location of most late clinical events after any dissection of the aorta. The rate of clinical events is much lower when all the dissected aorta has been removed in patients with AscAo dissection.

Levels of circulating procoagulant microparticles in nonvalvular atrial fibrillation.

Circulating procoagulant microparticles (MPs) arising from cell activation or fragmentation during apoptosis retain procoagulant properties and are increased in severe thrombotic states. We investigated whether circulating procoagulant MP levels would be increased in nonvalvular atrial fibrillation (AF). Using a hospital case-control study design, circulating procoagulant MP levels were measured in 45 patients with permanent and/or persistent AF who were not receiving anticoagulant therapy and 90 age-matched control subjects (45 with cardiovascular risk factors and 45 without). Annexin V-positive MP levels (expressed as nanomoles per liter of phosphatidylserine equivalent) were higher in patients with AF (median 9.3, interquartile range 6.8 to 17.3 nmol/L) than in control subjects with cardiovascular risk factors (median 4.9, interquartile range 3.7 to 8.4 nmol/L) and control subjects without cardiovascular risk factors (median 3.2, interquantile range 2.3 to 4.6 nmol/L; p<0.001). Platelet-derived MPs (captured with antiglycoprotein Ib) and endothelial-derived MPs (captured with anti-CD31) were similar in patients with AF and control subjects with cardiovascular risk factors but were significantly higher than in control subjects without cardiovascular risk factors. On multiple regression analysis, the presence of AF was a strong predictor of annexin V-positive MP level (p<.001). In conclusion, circulating procoagulant MPs are increased in persistent and/or permanent AF and might reflect a hypercoagulable state that could contribute to atrial thrombosis and thromboembolism.

Consequences of obstructive sleep apnoea syndrome on left ventricular geometry and diastolic function.

Obstructive sleep apnoea syndrome (OSAS) is a frequent sleep disorder that is known to be an independent risk factor for arterial hypertension (AHT). Potential confounding factors associated with both OSAS and AHT, such as age, diabetes mellitus and obesity, have been explored extensively, and are considered as independent but additive factors. However, these factors are also contributors to left ventricular (LV) hypertrophy (LVH) and LV diastolic dysfunction, both of which are important causes of cardiovascular morbidity, and have been reported to be associated with OSAS for decades. In this review, we present an overview of how OSAS may promote changes in LV geometry and diastolic dysfunction through its best-known cardiovascular complication, arterial hypertension. We also summarize the epidemiological links between OSAS and LVH, outline diastolic dysfunction in OSAS patients, and try to highlight the mechanisms responsible, focusing on the effect of confounding factors.

[Methods of development of recommendations for clinical practice (RCP) and of setting-up of a platform cancer heart vessels (PTF-CHV) in the inter3C Vaucluse-Arles]. / Méthodes d'élaboration des recommandations pour la pratique clinique (RPC) et fonctionnement de la plate forme cœur vaisseaux cancer (PTF-CVC) dans l'inter3C Vaucluse pays d'Arles.

Monitoring and prevention of cardiovascular complications of anti-neoplastic treatment are currently well known for anthracyclines and trastuzumab but remain poorly implemented. The management of cardiac and vascular side effects of targeted therapies is not codified. The purpose of the platform heart-vessel cancer is to optimize the management of such complications within a small area (Vaucluse region of Arles). The platform will offer prescribers an easily accessible database, doctors performing exams standardized monitoring forms and patients a uniform follow-up. We report here the methodology of the elaboration of recommendations for clinical practice and the ways to develop the platform. After a year of active process, an analysis of the will be performed to see opportunities for improvement and dissemination on a larger scale.

Left ventricular diastolic dysfunction in obstructive sleep apnoea syndrome by an echocardiographic standardized approach: An observational study.

BACKGROUND: The association between obstructive sleep apnoea syndrome (OSAS), left ventricular (LV) diastolic dysfunction and LV geometry remains controversial because of coexisting disorders. AIMS: To evaluate LV diastolic dysfunction and its independent predictors in a real-life cohort of OSAS patients, by a standardized approach. METHODS: We consecutively included 188 OSAS patients after an overnight polysomnography to undergo clinical evaluation, ambulatory blood pressure measurement and complete echocardiography, combining M-mode, two-dimensional Doppler and tissue Doppler imaging modes. Correlations between OSAS severity and clinical and echocardiographical variables were assessed, and logistic regression models were used to identify possible determining factors of LV diastolic dysfunction. RESULTS: Most patients were hypertensive (n=148, 78.7%) and already receiving treatment by continuous positive airway pressure (n=158, 84.5%). The prevalence of LV hypertrophy, defined by LV mass index (LVMi) normalized by height (2.7), was 12.4%, with a significant correlation with hypertension (P=0.004). The apnoea-hypopnoea index was correlated with body mass index (P<0.0001), 24-hour systolic blood pressure (P=0.01) and LVMi normalized by height (2.7) (P=0.03). Diastolic function assessed by a global approach was impaired for 70 patients (37.2%) and none of the OSAS severity variables was a determining factor after multivariable analysis with adjustment for age and sex. CONCLUSION: Diastolic dysfunction assessed by a standardized approach is common in OSAS and should be routinely evaluated; it is independently predicted by none of the respiratory severity variables.

HIV and coronary heart disease: time for a better understanding.

Cardiovascular disease, and particularly coronary heart disease, is an emerging area of concern in the HIV population. Since the advent of efficient antiretroviral therapies and the consequent longer patient life span, an increased risk for myocardial infarction has been observed in HIV-infected patients compared with the general population in Western countries. The pathophysiology of this accelerated atherosclerotic process is complex and multifactorial. Traditional cardiovascular risk factors-overrepresented in the HIV population-associated with uncontrolled viral replication and exposure to antiretroviral drugs (per se or through lipid and glucose disturbances) could promote acute ischemic events. Thus, despite successful antiviral therapy, numerous studies suggest a role of chronic inflammation, together with immune activation, that could lead to vascular dysfunction and atherothrombosis. It is time for physicians to prevent coronary heart disease in this high-risk population through the use of tools employed in the general population. Moreover, the lower median age at which acute coronary syndromes occur in HIV-infected patients should shift prevention to include patients <45 years of age. Available cardiovascular risk scores in the general population usually fail to screen young patients at risk for myocardial infarction. Moreover, the novel vascular risk factors identified in HIV-related atherosclerosis, such as chronic inflammation, immune activation, and some antiretroviral agents, are not taken into account in the available risk scores, leading to underestimation of cardiovascular risk in the HIV population. Cardiovascular prevention in HIV-infected patients is a challenge for both cardiologists and physicians involved in HIV care. We require new tools to assess this higher risk and studies to determine whether intensive primary prevention is warranted.

C-reactive protein and transesophageal echocardiographic markers of thromboembolism in patients with atrial fibrillation.

BACKGROUND: To determine whether C-reactive protein (CRP) in combination with a stroke risk stratification scheme can help in identifying transesophageal echocardiographic (TEE) markers of thromboembolism such as left atrial (LA)/left atrial appendage (LAA) thrombus, severe LA/LAA spontaneous echocardiographic contrast (SEC), and aortic plaque ≥ 4 mm. METHODS: Transthoracic echocardiography, TEE, and CRP measurement were performed at admission in 178 patients with non-valvular atrial fibrillation not receiving oral anticoagulant therapy. Patients were classified as at low, moderate, or high risk of thromboembolism based on seven clinical risk stratification schemes (SPAF, CHADS(2), Framingham, Birmingham/NICE, ACC/AHA/ESC 2006 guidelines, ACCP 2008, CHA(2)DS(2)VASc). RESULTS: Severe LA/LAA SEC, LA/LAA thrombus, and aortic plaque ≥ 4 mm were present in 6.2%, 6.7%, and 10.1% of patients, respectively. The combination of CRP with a cut-off value of 3.4 mg/L with the Birmingham/Nice or ACC/AHA/ESC 2006 risk score, led to a negative predictive value of 100% in low-risk patients and 91% in moderate-risk patients. For the detection of severe LA/LAA SEC or thrombus, a good discrimination (area under curve ≥ 0.70) using only clinical risk markers was observed for all classifications except for the Framingham and CHADS(2) risk scores. The addition of CRP did not improve the detection of LA/LAA SEC or thrombus, or of severe LA/LAA SEC, thrombus, or aortic plaque. CONCLUSION: The combination of clinical risk markers and CRP can help to exclude the presence of the TEE markers LA/LAA SEC or LA/LAA thrombus, particularly in patients classified at low or moderate risk of stroke.

Surgical management of patients with Marfan syndrome: evolution throughout the years.

AIM: To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome. METHODS: This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de référence national pour le syndrome de Marfan et apparentés and underwent a surgical event before or during follow-up in the centre. RESULTS: One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010. Aortic surgery was performed in 249 patients (22.7%; 20 children and 229 adults), including the Bentall procedure in 140 patients (56%) and valve-sparing surgery in 88 patients (35%); a supracoronary graft was performed in 19 patients (7.6%), usually for aortic dissection. During the past 20 years, the predominant reason for aortic surgery has switched from aortic dissection to aortic dilatation, while age at surgery has tended to increase (from 32.4 ± 11.9 years to 35.2 ± 12.4 years; P=0.075). Mitral valve surgery was performed in 61 patients (5.6%; six children and 55 adults), including 37 valvuloplasties (60.6%) and 18 mitral valve replacements (29.5%). No significant difference was observed when comparing mitral valve surgery before and after 2000. CONCLUSION: Surgery performed in patients with Marfan syndrome has switched from emergency surgery for aortic dissection to elective surgery for aortic dilatation; this is associated with surgery performed at an older age despite the indication for surgery having decreased from 60mm to 50mm. No significant evolution was observed for mitral valve surgery.

Cardiovascular findings and management in Turner syndrome: insights from a French cohort.

OBJECTIVE: Congenital cardiovascular malformations and aortic dilatation are frequent in patients with Turner syndrome (TS). The objective of this study was to investigate the cardiovascular findings and management in a large cohort of patients, including children and adults. DESIGN/METHODS: We recruited 336 patients with TS from a network of tertiary centers. We reviewed their files, checking for cardiovascular events, cardiac valve abnormalities, and aortic diameters indexed to body surface area (BSA) from magnetic resonance imaging (n=110) or echocardiography (n=300). RESULTS: Informative cardiovascular data were available for only 233 patients. Vascular surgery was reported in 7.4% of the cohort. The first cause of surgery was aortic coarctation, detected in 6.9% at a median age of 9.5 (range: 0-60) years. Bicuspid aortic valve (BAV) was detected in 21% at a median age of 20 years (25th-75th percentiles: 15-30). At least one aortic diameter exceeded 32 mm in 12% of the cohort. This was detected at a median age of 19 (7-30) years. When indexed to BSA, at least one aortic diameter exceeded 20 mm/m(2) in 39% of the cohort. CONCLUSION: Our study shows that cardiovascular monitoring for TS patients is currently insufficient in France. BAV is present at birth, but often remains undiagnosed until later in life. Therefore, improved management in cardiovascular monitoring is required and a more systematic approach should be taken.

Cardiac side effects of molecular targeted therapies: towards a better dialogue between oncologists and cardiologists.

Molecular targeted therapies (MTTs) have become a major component of modern management of various hematological and solid malignancies. However, some MTTs have been associated with cardiotoxicity. MTT-induced cardiovascular side effects include left ventricular systolic dysfunction, heart failure, conduction abnormalities, acute coronary syndrome, and hypertension. One of the most threatening complications of MTT, and notably of angiogenic inhibitors, is QT prolongation with the risk of torsades de pointe and sudden death. The precise incidence of cardiovascular events associated with MTT as well as their reversibility are unknown. Here, we summarize what is known about the cardiotoxicity of MTT, emphasizing MTTs that target tyrosine kinases. We have tried to provide both the basic mechanisms underlying specific cardiotoxicities (such as the interruption of specific signaling pathways leading to cardiomyocyte dysfunction and/or death), and offer guidance regarding the optimal way to detect and treat these cardiotoxicities.

Should all patients with non-valvular atrial fibrillation be anticoagulated?

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The prevalence and incidence of AF are rising, as confirmed in several European and American registries. Guidelines published in 2008 from the European Society of Cardiology/American Heart Association and from the American College of Chest Physicians, clarified the strategy of antithrombotic treatment in AF, which is based on the presence of risk factors for thromboembolism. This approach allows physicians to classify patients as at low, moderate or high risk, according to their individual risk characteristics, which are relatively similar in both sets of recommendations. Patients at moderate risk, however, who might justify anticoagulant or antiplatelet treatment, could be better characterized using morphological (echocardiographic) and/or biological factors or risk markers. Recent data have shown that the existence of a thrombogenic milieu in the left atrium (e.g., dilatation of the left atrial appendage and/or thrombus and/or spontaneous echocontrast and/or reduced emptying/filling flow velocity) indicates a higher risk of embolism and mortality. Furthermore, high-sensitivity C-reactive protein and haemostasis markers of coagulation are associated with thromboembolic risk and excess mortality in AF. Although current recommendations for the management of AF are not based on such markers, both could help physicians choose the optimal antithrombotic treatment (either vitamin K antagonists or antiplatelet drugs) according to the patient's specific risk profile. Nowadays, registries confirm under-prescription of vitamin K antagonist treatment in the 'real world,' even in patients at high thromboembolic risk, and over-prescription for at least one-third of low-risk patients. It is crucially important to realize that the risk of bleeding in patients with risk factors (e.g., older age, hypertension) is close to the risk of thromboembolism, which can have devastating outcomes in patients in AF. Alternative and efficient strategies (new oral anticoagulants, non-surgical closure of the left atrial appendage using percutaneous devices) are currently under investigation. Therefore reducing the risk of thromboembolism should be physicians' primary aim, particularly with the advent of alternative treatments and the development of new antithrombotic drugs such as oral thrombin and factor Xa inhibitors, which are currently being evaluated in clinical trials.

Factors influencing the level of circulating procoagulant microparticles in acute pulmonary embolism.

BACKGROUND: Flow cytometry has shown levels of platelet-derived microparticles (PMPs) and endothelial-derived microparticles (EMPs) to be elevated in deep-vein thrombosis. Cardiovascular risk factors can also contribute to hypercoagulability due to circulating procoagulant microparticles (CPMPs). AIMS: To investigate in a case-control study the respective contribution of pulmonary embolism and cardiovascular risk factors to the level of hypercoagulability due to CPMPs. METHODS: CPMP, PMP and EMP levels were measured in 45 consecutive patients (age 67.9 +/- 11.6 years; 66.7% men) admitted to an intensive care unit for acute pulmonary embolism (APE), 45 healthy control subjects with no history of venous thromboembolism or vascular risk factors (Controls(noCVRFs)), and 45 patients with cardiovascular risk factors (Controls(CVRFs)). APE was diagnosed by spiral computed tomography or scintigraphy. CPMP levels were assessed using a prothrombinase assay on platelet-depleted plasma (results expressed as nmol/L equivalent). RESULTS: CPMP levels were higher in APE patients than in Controls(noCVRFs) (medians 4.7 vs 3.2 nmol/L, interquartile ranges [IQRs] 2.9-11.1 vs 2.3-4.6 nmol/L; p=0.02). Similar results were reported for PMPs (medians 2.2 vs 1.9 nmol/L, IQRs 1.7-5.8 vs 1.4-2.4 nmol/L; p=0.02), whereas EMP levels were not significantly different. However, CPMP procoagulant activity was not significantly different in APE patients and Controls(CVRFs). CONCLUSIONS: CPMPs and PMPs were significantly elevated in APE patients vs Controls(noCVRFs), but this correlation was not significant when APE patients were compared with Controls(CVRFs). Our observations highlight the importance of adjusting for the presence of cardiovascular risk factors in conditions in which microparticle levels are raised.

Circulating procoagulant microparticles in acute pulmonary embolism: a case-control study.

We investigated whether circulating procoagulant microparticles (CPMPs) contributed to hypercoagulability in 45 patients with acute pulmonary embolism (APE) and in 45 controls with and 45 controls without cardiovascular risk factors. Concentrations of CPMPs and platelet-derived microparticles (PMPs) were statistically significantly higher in patients with APE than in controls without cardiovascular risk factors. PMPs appeared to be the main source of procoagulant microparticle release in APE, but this correlation disappeared when APE patients were compared to controls with cardiovascular risk factors. CPMPs may have a role in venous thrombosis as mediators of cardiovascular risk factors.

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study.

Compared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 microM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

Slow response to clopidogrel predicts low response.

OBJECTIVES: The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response. BACKGROUND: Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established. METHODS: We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action. RESULTS: Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049). CONCLUSIONS: Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity.

QT interval prolongation among patients treated with angiogenesis inhibitors.

Among toxicities associated with molecular targeted agents (MTA), cardiovascular toxicities remain largely unknown or underestimated. Their frequency is variable and dependent on the compound. A high incidence of hypertension, symptomatic or asymptomatic left ventricular systolic dysfunction, acute coronary syndrome, arterial and venous thrombosis has been observed in patients receiving MTA. One of the most threatening complications of angiogenic inhibitors (AI) could be QT prolongation with the risk of torsade de pointes (TdP) and sudden death. QT prolongation and torsade de pointes accounted for 29% of cardiac and non-cardiac post-marketing withdrawals. The assessment of the effects of drugs on cardiac repolarization is the subject of recent guidelines and recommendations. Regulatory agencies now require practically every new pharmaceutical compound to undergo a thorough investigation of its propensity to modify cardiac repolarization. To reduce the incidence of QT prolongation and torsade de pointes in patients receiving AI, cancer patients should be closely monitored while receiving AI.

Is the aortic root dilated in obstructive sleep apnoea syndrome?

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is associated with an increased risk of arterial hypertension (AH), coronary artery disease, atrial arrhythmias, heart failure, stroke and death. Whether OSAS influences aortic root size has not been fully investigated. The aim of our study was to investigate aortic root diameter and aortic stiffness in OSAS. METHODS: Using transthoracic Doppler echocardiography, we evaluated 76 patients with OSAS (mean age 52.7 +/- 9.5 years, 70 men [92%]) with no overt cardiovascular disease. The following parameters were measured offline: aortic diameter at Valsalva sinuses, aortic regurgitation (AR) grade, left ventricular (LV) mass, LV ejection fraction (LVEF, Simpson rule), systolic pulmonary artery pressure (sPAP). Aortic stiffness (carotid-femoral pulse wave velocity, PWV) was measured non-invasively using SphygmoCor technology. RESULTS: Mean duration of OSAS was four years and 84% of patients were being treated with continuous positive airway pressure. AH was documented in 39 (51%) patients. The mean aortic root diameter was 35.3 +/- 3.8 mm (26.9-44.6 mm) and the prevalence of aortic root dilatation was 3.9% (3 of 76 patients). On univariate analysis, age and sex were significant predictors of aortic root dilatation whereas arterial hypertension was not. CONCLUSIONS: The prevalence of aortic root enlargement was not increased in OSAS. Only age and sex and not arterial hypertension, were associated with aortic dilatation.

A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial.

OBJECTIVES: We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs). BACKGROUND: Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown. METHODS: Patients (n = 103) with non-ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated. RESULTS: Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group. CONCLUSIONS: In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.