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Biomedical subjects

Alec Vahanian

Publications and source records attributed to Alec Vahanian.

At least 19 recordsLinked to original sources
PubMed2008

A multi-perforated man: asymptomatic ruptured sinus of Valsalva aneurysm associated with an atrial and ventricular septal defect.

We report the case of an exceptional association of a right coronary sinus of Valsalva aneurysm (SVA) ruptured into the right ventricle, a supracristal ventricular septal defect (VSD) and an atrial septal defect (ASD). Our patient was totally asymptomatic and the diagnosis was established by echocardiography. The patient underwent prompt surgery that consisted in closing the aneurysm and the VSD with a pericardium patch.

Adult↗
PubMed2007

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. OBJECTIVE: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. DESIGN, SETTING, AND PATIENTS: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. INTERVENTIONS: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. MAIN OUTCOME MEASURES: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. RESULTS: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). CONCLUSION: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00091637.

Aged↗
PubMed2006

Three-dimensional evaluation of the mitral valve area and commissural opening before and after percutaneous mitral commissurotomy in patients with mitral stenosis.

AIMS: Management of patients with mitral stenosis (MS) relies on accurate evaluation of the mitral valve area (MVA). Planimetry (MVA(2D)) is considered as the reference method but must be performed at the tips of the leaflets with the correct plane orientation and therefore requires experienced operators. Real-time three-dimensional echocardiography (RT3DE) may overcome this limitation but its usefulness for experienced when compared with less experienced operators has not been evaluated. In addition, superiority of RT3DE for the evaluation of commissural splitting after percutaneous mitral commissurotomy (PMC) is unknown. METHODS AND RESULTS: 60 patients were prospectively evaluated by 2D and RT3DE before and after PMC by experienced operators. Before PMC, MVA(3D) was slightly higher than MVA(2D) (1.15 +/- 0.25 vs. 1.06 +/- 0.22 cm2, P = 0.0001) but correlation between methods was excellent (r = 0.73, P < 0.0001), mean difference was small (0.09 +/- 0.18 cm2) and clinically meaningless (three patients misclassified, two of whom had borderline MS severity). After PMC, MVA(3D) did not differ from and correlated well with MVA(2D) (1.87 +/- 0.37 vs. 1.85 +/- 0.32 cm2, P = 0.36; r = 0.76, P < 0.0001; mean difference 0.03 +/- 0.24 cm2). Twenty-five additional patients were also evaluated both by an experienced and a less experienced operators. Bland-Altman analysis showed the better agreement between MVA(3D) measured by the less experienced operator and MVA(2D) measured by the experienced operator than between MVA(2D) measured by the less experienced and the experienced operators (mean difference 0.03 +/- 0.34 vs. - 0.13 +/- 0.46 cm2, P = 0.03). When compared with RT3DE, 2DE underestimated the degree of commissural opening in 33% of patients and agreement between methods was weak (kappa = 0.41). CONCLUSION: RT3DE provides accurate MVA measurements similar to 2D planimetry performed by experienced operators. Thus, it does not provide a real advantage for experienced operators, whereas it seems particularly helpful for less experienced operators. In addition, RT3DE improves the description of valvular anatomy.

Angioplasty, Balloon, Coronary↗
PubMed2006

Evaluation of mitral valve area by the proximal isovelocity surface area method in mitral stenosis: could it be simplified?

AIM: One limitation for a wider use of the proximal isovelocity surface area method (PISA) for the evaluation of the mitral valve area (MVA) in patients with mitral stenosis (MS) is the requirement of an angle correction factor (angle alpha between the mitral leaflets) which cannot be obtained using the machine's built-in software and requires a manual measurement. The aim of the present study was to evaluate if the use of a fixed angle could provide an acceptable MVA estimation. METHODS AND RESULTS: In 48 patients (53 +/- 14 years, 75% female and 32% atrial fibrillation), MVA was prospectively measured by planimetry (MVA(2D)) and PISA (PISA(mes)). The angle alpha was manually measured on paper prints using a protractor. MVA(2D) was 1.38 +/- 0.56 cm(2) [0.5-2.40]. PISA(mes) (alpha = 104 +/- 13 degrees inter-quartiles 90-115) was 1.34 +/- 0.64 cm(2) [0.31-2.95] and did not differ from and correlated well with MVA(2D) (P = 0.25; r = 0.93, P < 0.0001). MVA estimated using the PISA method and a fixed angle value from 90 to 110 (MVA(alpha)(=90) to MVA(alpha)(=110)) progressively increased from 1.20 +/- 0.66 to 1.48 +/- 0.81 cm(2). Only MVA(alpha)(=100) (1.34 +/- 0.74 cm(2)) did not differ from and correlated well with both MVA(2D) and PISA(mes) (both P > 0.35 and r > 0.90, P < 0.0001). CONCLUSION: The angle formed by the mitral leaflet only slightly changes in between patients and use of a fixed angle value of 100 degrees provides an accurate estimation of the MVA by the PISA method in patients with MS. This simplification would facilitate and extend the use of the PISA as an additional method for the assessment of MS severity in routine practice.

Adult↗
PubMed2006

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

BACKGROUND: Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. METHODS: We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. RESULTS: The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). CONCLUSIONS: Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Aged↗
PubMed2006

Age, outcomes, and treatment effects of fibrinolytic and antithrombotic combinations: findings from Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 and ASSENT-3 PLUS.

BACKGROUND: Elderly patients with acute myocardial infarction are at particularly high risk for death and bleeding complications. The efficacy and safety of antithrombotic strategies in these patients remain unclear. METHODS: To provide more insight into the risk and benefit of antithrombotic strategies in the elderly, we examined patients from the ASSENT-3 and ASSENT-3 PLUS trials with STEMI who were treated with tenecteplase (TNK) and unfractionated heparin (UFH) or enoxaparin, or half-dose TNK with abciximab and reduced-dose UFH. RESULTS: Older patients had a higher risk profile, and lower use of concomitant therapies and revascularization procedures. We found an interaction between age and treatment effect for the efficacy end point (P = .0007) and the efficacy plus safety end point (P < .0001). Younger patients (<65 years) had a lower risk of the composite efficacy plus safety end point with enoxaparin (relative risk [RR] 0.84, 95% CI 0.74-0.94) or abciximab (RR 0.79, 95% CI 0.69-0.90) compared with UFH. In patients >65 years of age, the benefit of enoxaparin appeared to be offset by an increased risk of bleeding complications. The risk of the efficacy plus safety end point tended to be higher in elderly patients receiving abciximab and half-dose TNK (RR 1.18, 95% CI 0.91-1.51 for 76-85 years of age and RR 1.48, 95% CI 0.88-2.49 for >85 years of age). CONCLUSIONS: Although TNK with either enoxaparin or abciximab appeared to be more effective than with standard UHF in younger patients, these combinations tended to be less effective and even may be unsafe in the elderly. Development of new combination strategies and dosing schemes of fibrinolytics and antithrombotics with improved efficacy and safety in the elderly remains a high priority.

Aged↗
PubMed2005

Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery?

AIMS: To analyse decision-making in elderly patients with severe, symptomatic aortic stenosis (AS). METHODS AND RESULTS: In the Euro Heart Survey on valvular heart disease, 216 patients aged > or =75 had severe AS (valve area < or =0.6 cm(2)/m(2) body surface area or mean gradient > or =50 mmHg) and angina or New York Heart Association class III or IV. Patient characteristics were analysed according to the decision to operate or not. A decision not to operate was taken in 72 patients (33%). In multivariable analysis, left ventricular (LV) ejection fraction [OR = 2.27, 95% CI (1.32-3.97) for ejection fraction 30-50, OR = 5.15, 95% CI (1.73-15.35) for ejection fraction < or =30 vs. >50%, P = 0.003] and age [OR = 1.84, 95% CI (1.18-2.89) for 80-85 years, OR=3.38, 95% CI (1.38-8.27) for > or =85 vs. 75-80 years, P = 0.008] were significantly associated with the decision not to operate; however, the Charlson comorbidity index was not [OR = 1.72, 95% CI (0.83-3.50), P = 0.14 for index > or =2 vs. <2]. Neurological dysfunction was the only comorbidity significantly linked with the decision not to operate. CONCLUSION: Surgery was denied in 33% of elderly patients with severe, symptomatic AS. Older age and LV dysfunction were the most striking characteristics of patients who were denied surgery, whereas comorbidity played a less important role.

Age Factors↗
PubMed2005

Recommendations for the management of patients after heart valve surgery.

Approximately 50,000 valve replacement operations take place in Europe annually and almost as many valve repair procedures. Previous European guidelines on management of patients after valve surgery were last published in 1995 and were limited to recommendations about antithrombotic prophylaxis. American guidelines covering the broader topic of the investigation and treatment of patients with valve disease were published in 1998 but devoted relatively little space to post-surgical management. This document represents the consensus view of a committee drawn from three European Society of Cardiology (ESC) Working Groups (WG): the WG on Valvular Heart Disease, the WG on Thrombosis, and the WG on Rehabilitation and Exercise Physiology. In almost all areas of patient management after valve surgery, randomized trials and meta-analyses do not exist. Such randomized trials as do exist are very few in number, are narrowly focused with small numbers, have limited general applicability, and do not lend themselves to meta-analysis because of widely divergent methodologies and different patient characteristics. Recommendations are therefore almost entirely based on non-randomized studies and relevant basic science.

Anticoagulants↗
PubMed2005

Antithrombotic management after an ischemic stroke in French primary care practice: results from three pooled cross-sectional studies.

BACKGROUND AND PURPOSE: We aimed at quantifying and explaining the underuse of antithrombotic treatments after an ischemic stroke in patients seen in French primary care. METHODS: We pooled all ischemic stroke patients included in 3 observational primary care-based observational studies. French general practitioners and cardiologists recruited 14,544 patients with atherothrombotic disease including 4,322 with an ischemic stroke. Antithrombotic therapies and risk factors were prospectively recorded. Patients with atrial fibrillation (AF) were considered appropriate for oral anticoagulants (OAC) and those without AF for antiplatelet drugs. RESULTS: Out of the 4,322 stroke patients, 3,732 (86.3%) were taking at least one antithrombotic drug. Among the 765 patients with AF, 333 (43.5%) received OAC and 2,718 (86.9%) out of the 3,129 patients appropriate for antiplatelet drug were taking antiplatelet drug. Multivariate analyses did not single out any risk factors for nonuse of OAC and showed that female sex (OR = 1.48; IC 95%: 1.14-1.92) was associated with nonuse of antiplatelet drugs. Conversely, past myocardial infarction (OR = 0.44; IC 95%: 0.26-0.71) and hypercholesterolemia (OR = 0.64; IC 95%: 0.50-0.81) were associated with appropriate use of antiplatelet drugs. CONCLUSION: More than 50% of stroke patients with AF do not receive OAC and 15% of those without AF do not receive antiplatelet drugs. These findings are not satisfactorily explained by the main patients' characteristics and practitioner's speciality and underline the complexity of the process which allows the transfer of scientific evidence in clinical practice.

Adult↗
PubMed2005

Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors.

AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.

Adult↗
PubMed2005

Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial.

CONTEXT: In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. OBJECTIVE: To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. INTERVENTIONS: Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. MAIN OUTCOME MEASURES: The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. RESULTS: During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. CONCLUSIONS: The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.

Aged↗
PubMed2005

Echocardiographic evaluation of the mitral valve area before and after percutaneous mitral commissurotomy: the pressure half-time method revisited.

BACKGROUND: Doppler pressure half-time (PHT) is widely used for mitral valve area (MVA) assessment but its accuracy has not been fully evaluated before and after percutaneous mitral commissurotomy (PMC) in a large series of patients. METHODS: In 120 patients with severe mitral stenosis, MVA(PHT) was prospectively evaluated before and 24 to 48 hours after PMC and compared with 2-dimensional planimetry (MVA(2D)) as a reference method. RESULTS: After PMC, MVA(2D) significantly increased (1.81 +/- 0.30 vs 1.03 +/- 0.23 cm2, P < .0001), mean transmitral gradient decreased (5 +/- 3 vs 10 +/- 5 mm Hg, P < .0001), and a good valve opening (MVA(2D) > or = 1.5 cm2) was observed in 107 patients (89%). Before PMC, correlation between MVA(PHT) and MVA(2D) was only fair overall (r = 0.52, P < .0001) and weak in subgroups of older patients (> or = 60 years; r = 0.16, P = .37) and in patients in atrial fibrillation (r = 0.38, P < .05). After PMC, MVA(PHT) (1.62 +/- 0.39 cm2) was significantly lower than MVA(2D) (P < .0001) and correlation was poor overall (r = 0.30, P = .0004; mean difference 0.33 +/- 0.30 cm2) and in all subgroups (r < 0.35). However, for the prediction of a good valve opening, a PHT less than 130 milliseconds (observed in 43 patients, 36%) had an excellent specificity (100%) despite a poor sensitivity (44%). CONCLUSION: For MVA assessment, the PHT method should be used cautiously even before PMC, especially in older patients or those in atrial fibrillation. After PMC, it does not provide an accurate MVA evaluation but can still be used as a semiquantitative method: a PHT less than 130 milliseconds is associated with a good valve opening, which can be useful in difficult cases.

Anatomy, Cross-Sectional↗
PubMed2005

Percutaneous valve procedures: present and future.

Percutaneous mitral commissurotomy and aortic valvuloplasty have been being performed since the mid-1980s. Balloon commissurotomy has been used in thousands of cases worldwide and it provides good short- and long-term results in a wide range of patients. It has virtually replaced surgical commissurotomy in the treatment of mitral stenosis. In contrast, percutaneous aortic valvuloplasty is almost abandoned worldwide due to its lack of efficacy and the risks involved. The new techniques of percutaneous valve intervention: aortic valve replacement and mitral valve repair are at an early stage: the first in-man applications of these fledgling techniques started in 2002. Preliminary series show that they are feasible; however, they need to be further evaluated in comparison with contemporary treatment to assess accurately how efficient they are and the risks involved. Currently potential applications concern high-risk patients, however, in the future, after thorough evaluation, this may be extended to others. Thus, percutaneous interventions already play an important role in treatment of valvular heart disease, a role that seems set for future expansion.

Angiography↗