Jozef Bartunek

OLV Ziekenhuis Aalst, Alost, Flanders, Belgium

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Publications (201)1432.15 Total impact

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    ABSTRACT: Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P<0.05) apart from 10 μmol/L (P=0.077). Percentage inhibition was lower (P=0.048) in 6.3-kb α2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.
    Arteriosclerosis Thrombosis and Vascular Biology 04/2014; · 6.34 Impact Factor
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    ABSTRACT: The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, preclinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multimodality imaging, and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context.
    Journal of Cardiovascular Translational Research 03/2014; · 3.06 Impact Factor
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    ABSTRACT: The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n = 4086 coronary stenoses), in whom at least one stenosis was of intermediate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [-0.38 (95% CI: -0.41; -0.36); P < 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youden's index decreased from 0.28 to 0.11 for the overall population. The data confirm that one-third of a large patient population shows discordance between angiogram ≥50%DS and FFR ≤0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance.
    European Heart Journal 03/2014; · 14.10 Impact Factor
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    ABSTRACT: Information on exercise capacity and training in patients who underwent valvular surgery is scarce. The aim of this study is to evaluate postoperative exercise capacity and functional improvement after exercise training according to the preoperative risk and type of surgery. In this prospective study, 145 patients who underwent aortic valve surgery (AVS) or mitral valve surgery (MVS) and who were referred for cardiac rehabilitation were stratified according to the preoperative risk (European System for Cardiac Operative Risk Evaluation [EuroSCORE]) and type of surgery (sternotomy vs ministernotomy or port access). Exercise capacity was evaluated at the start and end of cardiac rehabilitation. Postoperative exercise capacity and the benefit from exercise training were compared between the groups. Patients with a higher preoperative risk had a worse postoperative exercise capacity, with a lower load, peak VO2, anaerobic threshold and 6-minute walking distance (all p <0.001), and a higher VE/VCO2 slope (p = 0.01). In MVS, port access patients performed significantly better at baseline (all p <0.05), but in AVS, ministernotomy patients performed better than sternotomy patients with a concomitant coronary artery bypass graft (p <0.05). Training resulted in an improvement in exercise capacity in each risk group and each type of surgery (all p <0.05). This gain in exercise capacity was comparable for the EuroSCORE risk groups and for the types of surgery, for patients after AVS or MVS. In conclusion, exercise capacity after cardiac surgery is related to the preoperative risk and the type of surgery. Despite these differences in postoperative exercise capacity, a similar benefit from exercise training is obtained, regardless of their preoperative risk or type of surgery.
    The American journal of cardiology 01/2014; · 3.58 Impact Factor
  • International journal of cardiology 01/2014; · 7.08 Impact Factor
  • Circulation 01/2014; 129(2):e21-2. · 15.20 Impact Factor
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    ABSTRACT: Objectives The aim of this study was to determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa inhibitor, compared with warfarin. Background In patients with atrial fibrillation, thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. Methods Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, we conducted a post-hoc analysis of patients undergoing cardioversion. Results A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those assigned to warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 ± 231 days and 251 ± 248 days, respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30-day follow-up period. Myocardial infarction occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). Conclusions Major cardiovascular events after cardioversion of atrial fibrillation are rare and comparable between warfarin and apixaban. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)
    Journal of the American College of Cardiology 01/2014; 63(11):1082–1087. · 14.09 Impact Factor
  • Journal of the American College of Cardiology 12/2013; 62(25):2454-6. · 14.09 Impact Factor
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    ABSTRACT: Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Stem cell retention was simulated in silico using 1- and 3-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol, a nickel and titanium alloy displaying shape memory and superelasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real-time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared with a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle without effect on biocompatibility or safety. Modeling-guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention.
    Circulation Cardiovascular Interventions 12/2013; · 6.54 Impact Factor
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    ABSTRACT: Monocyte-platelet aggregates (MPA) are increased in patients with acute coronary syndrome. We investigated whether MPA are associated with the presence of functionally significant coronary stenoses or with coronary arterial endothelial dysfunction. One hundred forty five patients undergoing elective coronary angiography were prospectively enrolled. Functional significance of coronary stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected patients underwent pacing protocol to evaluate Coronary endothelium-dependent vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with FFR ≤ 0.8 (FFRpos, n = 75), MPA did not significantly differ from FFR >0.8 patients (FFRneg, n = 70) (38.1 % [25.7-56.6] vs 34.0 % [20.5-49.9], p = 0.08). CVF was similar in FFRpos and FFRneg patients (percent vessel diameter change, %VDC = 7.19 % [6.01-10.9] vs 8.0 % [0.81-9.80], p = 0.78). Yet, patients with abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3 % [28.8-53.4] vs 20.5 % [17.0-32.9], p = 0.01). Moreover, MPA was inversely correlated with %VDC (R (2) = 0.26, p < 0.01). MPA levels are significantly higher in patients with abnormal coronary vasomotor function regardless of the presence of functionally significant coronary stenosis.
    Journal of Cardiovascular Translational Research 12/2013; · 3.06 Impact Factor
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    ABSTRACT: Drug-eluting stents (DES) are more effective than bare-metal stents (BMS) in small coronary vessel disease. Whether this is true in elderly patients, it is unclear, as frailty and a high rate of comorbidities could increase the rate of DES-related complications. To assess procedural and long-term clinical outcomes of elderly patients with small vessel disease treated with DES or BMS. Consecutive elderly patients (≥ 75 years old) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent<3mm) were recruited during 2004-2008. Procedural and long-term clinical outcomes were compared between patients treated with BMS and DES. Propensity score-adjusted logistic regression analysis was performed to account for potential selection bias. Among 293 patients (175 BMS, 118 DES), peri-procedural myocardial infarction (12 [7%] vs. 5 [4%]; P=0.35) and blood transfusions (3 [2%] vs. 0; P=0.08) were not significantly different between the BMS and DES groups. Clinical follow-up (96% of patients, median [interquartile range] follow-up 3.5 [2.4] years) showed significantly lower adjusted major adverse cardiac events (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.24-0.72; P=0.002) and target vessel revascularization (TVR) (HR 0.33, 95% CI 0.14-0.76; P=0.009) in the DES group. No significant differences were observed between the groups in terms of death, myocardial infarction, stent thrombosis or bleeding. In this retrospective, non-randomized analysis of the treatment of small vessel disease in elderly patients, DES were as safe and more effective than BMS with a significant reduction in TVR.
    Archives of cardiovascular diseases 11/2013; · 0.66 Impact Factor
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    ABSTRACT: Active myocarditis (AM) is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active AM, looking for accessible and valid early predictors of long-term prognosis. From 1981 to 2009, 82 patients with biopsy-proven AM were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points and/or presence of LVEF≥50%, was assessed. At baseline, left ventricular (LV) dysfunction (LVEF <50%) and left atrium enlargement were independently associated with long-term heart transplantation (HTx)-free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of NYHA III-IV classes, left atrium enlargement and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term revaluation showed a significant incremental prognostic value when compared to the baseline evaluation (baseline model vs 6 months model: Area Under the Curve 0.79 vs 0.90, p=0.03). Baseline LV function is a marker for prognosis regardless of the clinical pattern of disease onset and its reassessment at 6 months appears useful for assessing longer term outcome.
    Circulation 10/2013; · 15.20 Impact Factor
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    ABSTRACT: Fractional flow reserve (FFR)-guided percutaneous revascularization (percutaneous coronary intervention [PCI]) of intermediate stenosis in native coronary artery is safe and associated with better clinical outcomes as compared with an angiography-guided PCI. It is unknown whether this applies to coronary artery bypass grafts (CABGs). We included 223 patients with CABG and with stable or unstable angina and an intermediate stenosis involving an arterial or a venous graft. Patients were divided into 2 groups: FFR guided (n = 65, PCI performed in case of FFR ≤0.80) and angio guided (n = 158, PCI performed based on angiographic evaluation). Primary end point was major adverse cardiac and cerebrovascular event, defined as death, myocardial infarction, target vessel failure, and cerebrovascular accident (CVA). The 2 groups were similar in terms of demographic and clinical characteristics. Percutaneous coronary intervention was performed in 23 patients (35%) of the FFR-guided group and 90 patients (57%) of the angio-guided group (P < .01). In the FFR-guided group, PCI was more often performed in arterial grafts as compared with the angio-guided group (16 [70%] vs 12 [13%], respectively; P < .01). Follow-up was obtained in 96% of patients at a median of 3.8 years (1.6-4.0 years). At multivariate analysis, major adverse cardiac and cerebrovascular event rate was significantly lower in the FFR-guided group as compared with the angio-guided group (18 [28%] vs 77 [51%], hazard ratio 0.33 [0.11-0.96], P = .043]. Procedure costs were overall reduced in the FFR-guided group (€2240 ± €652 vs €2416 ± €522, P = .03). An FFR-guided PCI of intermediate stenosis in bypass grafts is safe and results in better clinical outcomes as compared with an angio-guided PCI. This clinical benefit is achieved with a significant overall reduction in procedural costs.
    American heart journal 07/2013; 166(1):110-8. · 4.65 Impact Factor
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    ABSTRACT: Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.
    Journal of Cardiovascular Translational Research 05/2013; · 3.06 Impact Factor
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    ABSTRACT: BACKGROUND: -We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF)Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. METHODS AND RESULTS: -The risk of a number of outcomes including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding or death ("net clinical benefit") were calculated in 3 patient groups: 1) No HF/no LVSD (n=8728) 2) HF/no LVSD (n=3207) and 3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24) and lowest in patients without HF or LVSD (1.54; 5.27); each comparison p<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death 0.89 (95% CI 0.81,0.98) p=0.02; for SSE, major bleed or death it was 0.85 (0.78,0.92); p<0.001. There was no heterogeneity of treatment-effect across the 3 groups. CONCLUSIONS: -Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
    Circulation Heart Failure 04/2013; · 6.68 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically-oriented mesenchymal stem cell therapy, and probe for efficacy signals in patients with chronic heart failure. BACKGROUND: In preclinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodelling. METHODS: The prospective, multicenter, randomized Cardiopoietic stem Cell therapy in heart failURE (C-CURE) trial was conducted in patients with heart failure of ischemic origin who received standard-of-care or standard-of-care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were carried out in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy. RESULTS: Mesenchymal stem cell cocktail-based priming was achieved for each patient with dose attained in 75%, and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (27.5±1.0 to 34.5±1.1%) versus standard-of-care alone (27.8±2.0 to 28.0±1.8%, p<0.0001), and was associated with a reduction in left ventricular end-systolic volume (-24.8±3.0 versus -8.8±3.9 mL, p<0.001). Cell therapy also improved the 6-min walk distance (+62±18 versus -15±20 m, p<0.01), and provided a superior composite clinical score encompassing cardiac parameters in tandem with NYHA functional class, quality of life, physical performance, hospitalization and event-free survival. CONCLUSIONS: The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signals of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial NCT00810238).
    Journal of the American College of Cardiology 04/2013; · 14.09 Impact Factor
  • Heart (British Cardiac Society) 03/2013; · 5.01 Impact Factor
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    ABSTRACT: Aims: Endothelium dysfunction has been reported in patients (pts) undergoing transradial catheterisation. Alterations of the hand microcirculation possibly associated with systemic inflammation have never previously been reported. We aimed at investigating possible alteration of hand endothelial microcirculation secondary to transradial heart catheterisation. Methods and results: We randomised 40 pts with stable angina undergoing coronary angiography to either transradial (TR, n=20) or transfemoral (TF, n=20) approach. At baseline (BL), 24 hours (24 hrs) and 30 days (FU: follow-up) after catheterisation we assessed: a) peripheral endothelial function (EndoScore [ES]) by peripheral arterial tonometry (EndoPAT); b) biomarkers of endothelial turnover (sE-Selectin) and inflammation (hs-CRP). No clinical or angiographic differences were observed between the two groups. At 24 hours, ES (BL: 0.42±0.27 vs. 24 hours: 0.27±0.19, p<0.05) significantly decreased in the TR group, but not in the TF group (BL: 0.44±0.34 vs. 24 hours: 0.45±0.39, n.s.). Both sE-Selectin and hs-CRP increased significantly at 24 hours in all pts. At 30 days, we observed in the TR group a restoration of ES (FU: 0.44±0.34, n.s. vs. BL; p<0.05 vs. 24 hours), while no difference was observed in the TF group. A reduction towards baseline was observed in both groups of sE-Selectin and hs-CRP. Conclusions: A transient impairment of the digital microcirculatory endothelial function is observed in patients undergoing transradial diagnostic catheterisation, beyond local mechanical injury at the arterial access and on top of the systemic inflammatory response associated with heart catheterisation.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 03/2013; 8(11):1252-8. · 3.17 Impact Factor
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    ABSTRACT: BACKGROUND.: Previous studies failed to assess the individual prognostic role of thrombus aspiration (TA) or abciximab in primary percutaneous coronary intervention (pPCI), due their prevalent combined use. METHODS AND RESULTS.: A total of 644 consecutive STEMI patients treated with pPCI were included in this retrospective registry from January 2006 to December 2008. Patients were divided in: a) Group 1, with conventional pPCI; b) Group 2, with pPCI and abciximab; c) Group 3, with pPCI and TA; d) Group 4, with pPCI and abciximab plus TA. Primary end point was the composite of major adverse cardiovascular events (MACE, defined as overall mortality, myocardial infarction, target vessel revascularization, and major bleedings) at one year. Baseline clinical and angiographic characteristics were not different among the groups, with the exception of a younger age in group 4. The 2 groups of patients treated with thrombus aspiration (group 3 and 4) received more frequently direct stenting (p<0.001 vs. group 1 for both), presented higher rate of end-procedural TIMI flow grade 3 (p<0.001 vs. group 1 for both), and lower rate of no-reflow (p=0.016 and p<0.001 vs. group 1, respectively). Patients of group 2 presented a borderline non-significant trend toward higher rate of end-procedural TIMI flow grade 3 (p=0.083 vs. group 1). MACEs at one year were 43 (29%) in group 1 vs. 25 (22%) in group 2 vs. 24 (19%) in group 3 vs. 32 (13%) in group 4 (log-rank p=0.001). At the multivariate Cox regression analysis, combined TA plus abciximab in group 4 (HR: 0.48, CI 95% 0.28-0.84, p=0.01) and a higher left ventricular ejection fraction (HR: 0.97, CI 95% 0.95-0.98, p<0.001) were significantly associated with lower MACE rate. CONCLUSIONS.: The combination of pharmacologic and mechanic antithrombotic treatment during pPCI was associated with better 1-year clinical outcome. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 01/2013; · 2.51 Impact Factor
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    ABSTRACT: This manuscript reviews the studies performed with ALX-0081 (INN: caplacizumab), a Nanobody targeting von Willebrand factor, in the context of current antithrombotic therapy in coronary artery disease. ALX-0081 specifically inhibits platelet adhesion to the vessel wall, and may control platelet aggregation and subsequent clot formation without increasing bleeding risk. A substantial number of antithrombotics are aimed at this cascade; however, their generally indiscriminative mode of action can result in a narrow therapeutic window, defined by the risk for bleeding complications, and thrombotic events. Nonclinically, ALX-0081 compared favorably to several antithrombotics. In Phase I studies in healthy subjects and stable angina patients undergoing percutaneous coronary intervention (PCI), ALX-0081 was well tolerated, and effectively inhibited pharmacodynamic markers. Following these results, a phase II study was initiated in high-risk acute coronary syndrome patients undergoing PCI. Based on its mechanism of action, ALX-0081 is also being developed for acquired thrombotic thrombocytopenic purpura.
    Journal of Cardiovascular Translational Research 01/2013; · 3.06 Impact Factor

Publication Stats

4k Citations
1,432.15 Total Impact Points

Institutions

  • 1994–2014
    • OLV Ziekenhuis Aalst
      Alost, Flanders, Belgium
  • 2013
    • Université Paris Descartes
      Lutetia Parisorum, Île-de-France, France
  • 2012–2013
    • Università degli Studi di Trieste
      Trst, Friuli Venezia Giulia, Italy
    • University of Glasgow
      • • BHF Glasgow Cardiovascular Research Centre
      • • Institute of Cardiovascular and Medical Sciences
      Glasgow, SCT, United Kingdom
  • 2011
    • Klinički centar Srbije
      Beograd, Central Serbia, Serbia
  • 2010
    • Mayo Foundation for Medical Education and Research
      • Division of Cardiovascular Diseases
      Scottsdale, AZ, United States
  • 2007–2010
    • University Hospital of Lausanne
      • Service de cardiologie
      Lausanne, Vaud, Switzerland
    • Fakultní nemocnice Královské Vinohrady
      Praha, Praha, Czech Republic
    • Cardiovascular Research Foundation
      New York City, New York, United States
  • 2008–2009
    • The National Institute of Cardiovascular Diseases
      Presburg, Bratislavský, Slovakia
  • 2006
    • Ghent University
      • Cardiology
      Gent, VLG, Belgium
  • 2005
    • University of Naples Federico II
      • Department of Advanced Biomedical Sciences
      Napoli, Campania, Italy
  • 2001
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
  • 1997–2000
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, MA, United States
  • 1999
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
  • 1996
    • Detská fakultná nemocnica s poliklinikou v Bratislave
      Presburg, Bratislavský, Slovakia