Jozef Bartunek

OLV Ziekenhuis Aalst, Alost, Flanders, Belgium

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Publications (218)1557.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR). IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR. Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2010; 5(8):939-45. · 3.17 Impact Factor
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    ABSTRACT: The mature, biologically active 32-amino acid long B-type natriuretic peptide (BNP(1-32)), is cleaved by corin from the BNP prohormone. Recent data demonstrated that BNP(1-32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase (DPP) IV. DPP IV removes the two amino-terminal amino acids (Ser and Pro) from BNP(1-32) to produce BNP(3-32), which has been detected in plasma of patients with heart failure. In a canine model, intravenous BNP(3-32) infusion resulted in less natriuresis, diuresis and vasodilation compared to intravenous infusion of BNP(1-32). The clinical relevance of these observations may be important for patients with high plasma BNP concentrations, which can be measured by commercially available immunoassays. Further studies are needed to explore whether DPP IV inhibitors increase the bioavailability of BNP(1-32), delay the progression of heart failure and increase the efficacy of exogenously administered BNP(1-32) in decompensated heart failure.
    Biomarkers in Medicine 04/2010; 4(2):315-20. · 3.22 Impact Factor
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    ABSTRACT: The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly. This document provides suggested guidance in 4 methods of delivery: endocardial, intracoronary, coronary sinus, and epicardial.
    JACC. Cardiovascular Interventions 03/2010; 3(3):265-75. · 1.07 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the correlation between myocardial ischemia detected by myocardial perfusion imaging (MPI) with single-photon emission computed tomography with intracoronary pressure-derived fractional flow reserve (FFR) in patients with multivessel coronary disease at angiography. Myocardial perfusion imaging can underestimate the number of ischemic territories in patients with multivessel disease. However, there are limited data comparing MPI and FFR, a highly accurate functional index of myocardial ischemia, in multivessel coronary disease. Sixty-seven patients (201 vascular territories) with angiographic 2- or 3-vessel coronary disease were prospectively scheduled to undergo within 2 weeks MPI (rest/stress adenosine) and FFR in each vessel. In 42% of patients, MPI and FFR detected identical ischemic territories (mean number of territories 0.9 +/- 0.8 for both; p = 1.00). In the remaining 36% MPI underestimated (mean number of territories; MPI: 0.46 +/- 0.6, FFR: 2.0 +/- 0.6; p < 0.001) and in 22% overestimated (mean number of territories; MPI: 1.9 +/- 0.8, FFR: 0.5 +/- 0.8; p < 0.001) the number of ischemic territories in comparison with FFR. There was poor concordance between the ability of the 2 methods to detect myocardial ischemia on both a per-patient (kappa = 0.14 [95% confidence interval: -0.10 to 0.39]) and per-vessel (kappa = 0.28 [95% confidence interval: 0.15 to 0.42]) basis. Myocardial perfusion imaging with single-photon emission computed tomography has poor concordance with FFR and tends to underestimate or overestimate the functional importance of coronary stenosis seen at angiography in comparison with FFR in patients with multivessel disease. These findings might have important consequences in using MPI to determine the optimal revascularization strategy in patients with multivessel coronary disease.
    JACC. Cardiovascular Interventions 03/2010; 3(3):307-14. · 1.07 Impact Factor
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    ABSTRACT: Platelet reactivity is greater in patients with stable angina and with more extensive peripheral vascular atherosclerosis. We sought to evaluate whether impaired peripheral microcirculatory endothelial function might correlate with platelet reactivity after clopidogrel and therefore predispose to an unfavorable outcome after percutaneous coronary intervention (PCI). In 52 consecutive patients with stable angina undergoing elective PCI, endothelial function was assessed by (1) endothelial peripheral arterial tonometry (measuring the "Endoscore"); (2) the von Willebrandt factor antigen level and ristocetin co-factor activity. Basal platelet reactivity was assessed by soluble P-selectin. Patients then received a 600-mg clopidogrel loading dose > or = 12 hours before PCI. A blood sample was withdrawn 12 hours later, but before PCI, to assess platelet reactivity using the P2Y12 reaction unit and percentage of P2Y12 inhibition with the point-of-care VerifyNow P2Y12 assay. Troponin T was assessed 24 hours after PCI. The Endoscore inversely correlated with von Willebrandt factor antigen activity (r = -0.52, p = 0.0001) and soluble P-selectin concentration (r = -0.36, p = 0.021), suggesting greater platelet reactivity with increased impaired endothelial function. After clopidogrel, the Endoscore correlated directly with the percentage of P2Y12 inhibition (r = 0.36, p = 0.009) and inversely with the P2Y12 reaction unit (r = -0.41, p = 0.002), suggesting greater residual platelet reactivity with more impaired endothelial function. The average Endoscore was significantly lower in patients with troponin T elevation (troponin positive group 0.267 + or - 0.091) than in patients without troponin T elevation (troponin negative group 0.508 + or - 0.041, p = 0.015 vs troponin positive). In conclusion, an impaired endothelial response before clopidogrel was associated with greater platelet reactivity after clopidogrel. This link might explain the unfavorable PCI outcomes in patients with more severe endothelial impairment.
    The American journal of cardiology 02/2010; 105(3):333-8. · 3.58 Impact Factor
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    ABSTRACT: Platelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet alpha2A-(alpha2A-AR) and beta2-adrenergic receptor (beta2-AR) stimulation. It was the objective of this study to assess the potential influence of alpha2A-AR and beta2-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3/6.7 kb alpha2A-AR polymorphism, and for Arg16Gly and Gln27Glu beta2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 micromol-induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A slight though negligible association was found between 6.3 kb allele of alpha2A-AR with platelet reactivity ADP-Ag induced (beta: -2.91 [-5.68;-0.14], p=0.04). A borderline not significant reduction in PRI VASP was observed in 6.3 kb alpha2A-AR carriers (beta: -3.81 [-0.09;7.72], p=0.06). No significant effect on platelet parameters was observed for the other tested polymorphisms. Common alpha2A- and beta2-adrenergic receptor polymorphisms do not show any major impact on residual platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with 250 mg aspirin and 600 mg clopidogrel is administered.
    Thrombosis and Haemostasis 02/2010; 103(4):774-9. · 5.76 Impact Factor
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    ABSTRACT: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs. Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls. Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 +/- 0.01, mean +/- SEM) and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 +/- 0.2 vs 6.1 +/- 0.8, mmHg/ml, p < 0.001) and end-systolic elastance to effective arterial elastance ratio (0.6 +/- 0.1 vs 1.4 +/- 0.2, p < 0.001), with altered active relaxation (dP/dtmin -1992 +/- 71 vs -2821 +/- 305, mmHg/s, p < 0.01) but preserved left ventricular capacitance (70 +/- 6 vs 61 +/- 3, ml at 20 mmHg, p = NS) and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin. In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function.
    BMC Cardiovascular Disorders 01/2010; 10:32. · 1.46 Impact Factor
  • Heart Lung &amp Circulation 01/2010; 19. · 1.25 Impact Factor
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    ABSTRACT: We tested the hypothesis that residual platelet reactivity after clopidogrel correlates with the extent and severity of coronary atherosclerosis in patients undergoing elective percutaneous coronary intervention (PCI). Platelets are actively involved in vascular atherosclerosis. We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego, California). High platelet reactivity (HPR) was defined as PRU value >or=240. Presence of multivessel disease (MVD) and total stent length (TSL) were used as surrogate markers of atherosclerosis severity and extension. Patients with MVD showed higher PRU compared with single-vessel disease (SVD) patients (222 +/- 85 vs. 191 +/- 73; p < 0.001). The PRU increased with the number of stenotic coronaries (1-vessel disease: 191 +/- 73; 2-vessel disease: 220 +/- 88; 3-vessel disease: 226 +/- 80; p = 0.002). The PRU was higher in the third TSL tertile compared with first tertile (217 +/- 83 vs. 191 +/- 73; p = 0.048). The HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs. 22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first tertile; p = 0.020). By multivariate analysis, HPR was the only independent predictor of periprocedural myocardial infarction (p = 0.034). Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI.
    JACC. Cardiovascular Interventions 01/2010; 3(1):35-40. · 1.07 Impact Factor
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    ABSTRACT: Stem cell therapy can facilitate cardiac repair in infarcted myocardium, but the optimal cell type remains uncertain. We conducted a randomized, blind, and placebo-controlled comparison of autologous bone marrow mononuclear cell and mesenchymal stem cell therapy in a large-animal model of chronic myocardial infarction. Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of mononuclear cells (227.106 +/- 32.106 cells), mesenchymal stem cells (232.106 +/- 40.106 cells), or placebo (n = 8 per group). Cardiac performance and remodeling were assessed up to 16 weeks' follow-up. At echocardiographic analysis, the wall motion score index showed a sustained improvement after mononuclear cell transfer (from 1.8 +/- 0.1 to 1.5 +/- 0.07) and a moderate late improvement after mesenchymal stem cell transfer (from 1.9 +/- 0.08 to 1.7 +/- 0.1). After mononuclear cell transfer, end-systolic elastance increased (from 2.23 +/- 0.25 to 4.42 +/- 0.55 mm Hg/mL), infarct size decreased (from 13% +/- 0.67% to 10% +/- 1.17%), N-terminal B-type natriuretic propeptide level decreased (from 608 +/- 146 to 353 +/- 118 pmol/L), and relative wall area and arterial density increased. Vascular endothelial growth factor receptor 2 expression was upregulated in the border zone. No change in cardiac contractility or histologic parameters was noted in the mesenchymal stem cell group. In a canine model of chronic myocardial infarction, bone marrow mononuclear cell transfer is superior to mesenchymal stem cell transfer in improvement of cardiac contractility and regional systolic function and reduction in infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favorable angiogenic environment and neovascularization.
    The Journal of thoracic and cardiovascular surgery 10/2009; 138(3):646-53. · 3.41 Impact Factor
  • Jozef Bartunek
    Biomarkers in Medicine 10/2009; 3(5):435-7. · 3.22 Impact Factor
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    ABSTRACT: Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR. In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was > or =0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; n=138). When FFR was <0.80, coronary artery bypass grafting was performed (surgical group; n=75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (P=0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P=0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (r=-0.38, P<0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis <50%, the left main coronary artery stenosis was hemodynamically significant by FFR. In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made "blindly" about the need for revascularization.
    Circulation 09/2009; 120(15):1505-12. · 15.20 Impact Factor
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    ABSTRACT: The persistence of moderate ischemic mitral regurgitation (IMR) after isolated coronary artery bypass graft surgery is an important independent predictor of long-term mortality. The aim of the present study was to identify predictors of postoperative improvement in moderate IMR in patients with ischemic heart disease undergoing elective isolated coronary artery bypass graft surgery. The study population consisted of 135 patients with ischemic heart disease (age, 65+/-9 years; 81% male) and moderate IMR undergoing isolated coronary artery bypass graft surgery. Fourteen patients died before the 12-month follow-up echocardiography and were excluded. At the 12-month follow-up, 57 patients showed no or mild IMR (improvement group), whereas 64 patients failed to improve (failure group). Before coronary artery bypass graft surgery, the improvement group had significantly more viable myocardium and less dyssynchrony between papillary muscles than the failure group (P<0.001). All other preoperative parameters were similar in both groups. Large extent (> or =5 segments) of viable myocardium (odds ratio, 1.45; 95% confidence interval, 1.22 to 1.89; P<0.001) and absence (<60 ms) of dyssynchrony (odds ratio, 1.49; 95% confidence interval, 1.29 to 1.72; P<0.001) were independently associated with improvement in IMR. The majority (93%) of patients with viable myocardium and an absence of dyssynchrony showed an improvement in IMR. In contrast, only 34% and 18% of patients with dyssynchrony and nonviable myocardium, respectively, showed an improvement in IMR, whereas 32% and 49%, respectively, of these patients showed worsening of IMR (P<0.001). Reliable improvement in moderate IMR by isolated coronary artery bypass graft surgery was observed only in patients with concomitant presence of viable myocardium and absence of dyssynchrony between papillary muscles.
    Circulation 09/2009; 120(15):1474-81. · 15.20 Impact Factor
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    ABSTRACT: To evaluate efficacy of percutaneous ultrasound-guided thrombin injection (UGTI) of iatrogenic femoral artery pseudoaneurysm (PSA) and to identify the risk factors associated with PSA recurrence. We treated 140 patients aged 76 years (range 49-83) presented with femoral artery PSA after cardiac catheterisation by percutaneous UGTI (500 IU/ml solution of activated human thrombin). Factors associated with the recurrence of PSA were analysed. One hundred nineteen patients were successfully treated by one injection of thrombin (immediate success rate 85%). In 19 patients (13.6%), short local compression following injection was needed for complete occlusion (overall success rate 98.6%, 138/140). In one case, progression of PSA required conversion to surgery (0.7%). In one patient with pre-existing stenosis of superficial femoral artery, acute limb ischaemia developed after UGTI (0.7%). The recurrence of PSA in 30-days follow-up (10 patients, 7%) was associated with obesity (BMI>30, OR=1.39, 95% CI 1.09-1.78, p<0.05), and with extensive combination of anti-aggregation and anti-coagulation therapy (OR=2.11, 95% CI 1.23-3.62, p<0.0001) as revealed by both univariate and multivariate analysis. The UGTI is a safe and effective treatment of iatrogenic femoral artery PSA. Recurrence is low and associated with obesity and extensive use of combined anti-aggregation and anti-coagulation therapy.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 09/2009; 5(4):443-7. · 3.17 Impact Factor
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    ABSTRACT: We assessed the safety and feasibility of permanent implantation of a novel coronary sinus mitral repair device (PTMA, Viacor Inc). Symptomatic (New York Heart Association class 2 or 3) patients with primarily functional mitral regurgitation (MR) were included. A diagnostic PTMA procedure was performed in the coronary sinus venous continuity. MR was assessed and the PTMA device adjusted to optimize efficacy. If MR reduction (> or =1 grade) was observed, placement of a PTMA implant was attempted. Implanted patients were evaluated with echocardiographic, quality of life, and exercise capacity metrics. Nineteen patients received a diagnostic PTMA study. Diagnostic PTMA was effective in 13 patients (MR grade 3.2+/-0.6 reduced to 2.0+/-1.0), and PTMA implants were placed in 9 patients. Four devices were removed uneventfully (7, 84, 197, and 216 days), 3 for annuloplasty surgery due to observed PTMA device migration and/or diminished efficacy. No procedure or device-related major adverse events with permanent sequela were observed in any of the diagnostic or implant patients. Sustained reductions of mitral annulus septal-lateral dimension from 3D echo reconstruction dimensions were observed (4.0+/-1.2 mm at 3 months). Percutaneous implantation of the PTMA device is feasible and safe. Acute results demonstrate a possibly meaningful reduction of MR in responding patients. Sustained favorable geometric modification of the mitral annulus has been observed, though reduction of MR has been limited. The PTMA method warrants continued evaluation and development.
    Circulation Cardiovascular Interventions 08/2009; 2(4):277-84. · 6.54 Impact Factor
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    ABSTRACT: Myocardial viability and left ventricular dyssynchrony are important predictors of long-term outcomes in patients with ischemic left ventricular dysfunction. The objective of this study was to test the hypothesis that assessment of myocardial viability and left ventricular dyssynchrony will predict perioperative mortality in high-risk patients with ischemic left ventricular dysfunction having coronary artery bypass surgery. The study consisted of 79 consecutive patients with ischemic cardiomyopathy (age 65 +/- 9 years; 81% men; ejection fraction 30% +/- 6%) and logistic European system for cardiac operative risk evaluation > 10% having coronary artery bypass surgery. Myocardial viability was assessed by delayed contrast-enhanced magnetic resonance imaging. Left ventricular dyssynchrony was calculated using tissue Doppler from measurements of regional electromechanical coupling times in left ventricular basal segments before coronary artery bypass surgery. Twenty (25.3%) patients died within 30 days following coronary artery bypass surgery. Survivors (n = 59) showed a larger extent of viable myocardium (6.9 +/- 3.6 viable segments vs 3.4 +/- 3.3 viable segments, P < .001) and smaller left ventricular dyssynchrony (75 +/- 5 ms vs 179 +/- 83 ms, P < .001) than nonsurvivors. The presence of significant dyssynchrony (>or=105 ms) and absence of myocardial viability (<5 viable segments) independently predicted 30-day mortality with hazard ratio 3.26, 95% confidence interval 1.61 to 8.33 (P < .01) and hazard ratio 1.72, 95% confidence interval 1.59 to 1.89 (P < .01), respectively. All but 2 patients (94.1%) with viable myocardium and without left ventricular dyssynchrony survived coronary artery bypass surgery as compared with only 12 (52.2%) patients with nonviable myocardium and severe dyssynchrony (P < .001). In high-risk patients with ischemic left ventricular dysfunction having coronary artery bypass surgery, both myocardial viability and left ventricular dyssynchrony are important predictors of perioperative outcome. Assessment of myocardial viability and left ventricular dyssynchrony should be a routine part of the preoperative evaluation of these patients.
    The Journal of thoracic and cardiovascular surgery 08/2009; 138(1):62-8. · 3.41 Impact Factor
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    ABSTRACT: Our purpose was to evaluate the appropriateness of multidetector computed tomography angiography (MDCTA) as an anatomical standard for decision making in patients with known or suspected coronary artery disease. Although correlative studies between MDCTA and coronary angiography (CA) show good agreement, MDCTA visualizes plaque burden and calcifications well before luminal dimensions are encroached. Pressure-derived fractional flow reserve (FFR) was obtained in 81 patients (116 vessels) who underwent both CA and MDCTA. Segments were visually graded for stenosis severity as: G0 = normal, G1 = nonobstructive (<50% diameter reduction), and G2 = obstructive (> or =50% diameter reduction). Concordance between segmental severity scores by MDCTA and CA was good (k = 0.74; 95% confidence interval: 0.56 to 0.92). Diagnostic performance of MDCTA for detection of functionally significant stenosis based on FFR was low (sensitivity 79%; specificity 64%; positive likelihood ratio 2.2; negative likelihood ratio 0.3). Revascularization was considered appropriate in the presence of reduced FFR (< or =0.75). Decision making based on MDCTA guidance would result in revascularization in the absence of ischemia in 22% of patients (18 of 81) and inappropriate deferral in 7% (6 of 81), while revascularization in the absence of ischemia would be 16% (13 of 81) and inappropriate deferral 12% (10 of 81) with decisions guided by CA. Combined evaluation of stenosis severity using both anatomy (with either CA or MDCTA) and function (with FFR) yields the highest proportion of appropriate decisions: 90% and 91%, respectively (p = 0.0001 vs. CA only, p = 0.0001 vs. MDCTA only). Similar to CA, anatomical assessment of coronary stenosis severity by MDCTA does not reliably predict its functional significance.
    JACC. Cardiovascular Interventions 06/2009; 2(6):550-7. · 1.07 Impact Factor
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    ABSTRACT: The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in its pathogenesis. However, with the knowledge that 75% of the number of cells in the heart are nonmyocytes, it is important to determine whether the apoptosis in HF is occurring in myocytes or in nonmyocytes. We studied both a nonhuman primate model of chronic HF, induced by rapid pacing 2-6 mo after myocardial infarction (MI), and biopsies from patients with ischemic cardiomyopathy. Dual labeling with a cardiac muscle marker was used to discriminate apoptosis in myocytes versus nonmyocytes. Left ventricular ejection fraction decreased following MI (from 78% to 60%) and further with HF (35%, P < 0.05). As expected, total apoptosis was increased in the myocardium following recovery from MI (0.62 cells/mm(2)) and increased further with the development of HF (1.91 cells/mm(2)). Surprisingly, the majority of apoptotic cells in MI and MI + HF, and in both the adjacent and remote areas, were nonmyocytes. This was also observed in myocardial biopsies from patients with ischemic cardiomyopathy. We found that macrophages contributed the largest fraction of apoptotic nonmyocytes (41% vs. 18% neutrophils, 16% fibroblast, and 25% endothelial and other cells). Although HF in the failing human and monkey heart is characterized by significant apoptosis, in contrast to current concepts, the apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes.
    AJP Heart and Circulatory Physiology 05/2009; 297(2):H785-91. · 4.01 Impact Factor
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    ABSTRACT: This study aimed to evaluate the degradation rate and long-term vascular responses to the absorbable metal stent (AMS). The AMS demonstrated feasibility and safety at 4 months in human coronary arteries. The PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting) was a prospective, multicenter clinical trial of 63 patients with coronary artery disease who underwent AMS implantation. Angiography and intravascular ultrasound (IVUS) were conducted immediately after AMS deployment and at 4 months. Eight patients who did not require repeat revascularization at 4 months underwent late angiographic and IVUS follow-up from 12 to 28 months. The AMS was well-expanded upon deployment without immediate recoil. The major contributors for restenosis as detected by IVUS at 4 months were: decrease of external elastic membrane volume (42%), extra-stent neointima (13%), and intra-stent neointima (45%). From 4 months to late follow-up, paired IVUS analysis demonstrated complete stent degradation with durability of the 4-month IVUS indexes. The neointima was reduced by 3.6 +/- 5.2 mm(3), with an increase in the stent cross sectional area of 0.5 +/- 1.0 mm(2) (p = NS). The median in-stent minimal lumen diameter was increased from 1.87 to 2.17 mm at long-term follow-up. The median angiographic late loss was reduced from 0.62 to 0.40 mm by quantitative coronary angiography from 4 months to late follow-up. Intravascular ultrasound imaging supports the safety profile of AMS with degradation at 4 months and maintains durability of the results without any early or late adverse findings. Slower degradation is warranted to provide sufficient radial force to improve long-term patency rates of the AMS.
    JACC. Cardiovascular Interventions 05/2009; 2(4):312-20. · 1.07 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) is common after heart transplantation (HTx). This study assessed the influence of CKD on exercise capacity and ventilatory efficiency after HTx. This cross-sectional study included 79 HTx patients (age 64 +/- 10 years, 66 men) at 8.1 +/- 4.3 years post-HTx who underwent maximal exercise testing, cardiac function assessment, and blood analysis. According to estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)), patients were categorized as having severe (Group 1, GFR < or = 30; n = 15), moderate (Group 2, GFR 30-60; n = 40), and mild (Group 3, GFR > 60; n = 24) renal impairment. Patients in Group 1 were older, had lower peakVO(2) and impaired ventilatory efficiency compared with Groups 2 and 3 (all p < 0.05) Peak Watts, peak ventilation, and peak heart rate were lower in Group 1 compared with Group 3 (all p < 0.05). Exercise-derived variables did not differ significantly between Groups 2 and 3. GFR correlated with peakVO(2)/kg (r = 0.47; p < 0.01) and peak Watts (r = 0.34, p < 0.01). GFR (adjusted r(2) = 0.34), mean arterial pulmonary pressure, and age were the strongest independent predictors of peakVO(2). The proposed model explained 48% of variability in peakVO(2). By receiver operator characteristic analysis, eGFR was superior in distinguishing patients with impaired from those with preserved exercise capacity (peakVO(2) < 18 vs > 18 ml/kg/min). Chronic KD after HTx is associated with impaired maximal exercise capacity and decreased ventilatory efficiency. GFR is a strong independent non-exercise-derived predictor of peak VO(2) in these patients.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2009; 28(5):446-52. · 3.54 Impact Factor

Publication Stats

5k Citations
1,557.05 Total Impact Points

Institutions

  • 1994–2014
    • OLV Ziekenhuis Aalst
      Alost, Flanders, Belgium
  • 2013
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • Uppsala University
      • UCR-Uppsala Clinical Research center
      Uppsala, Uppsala, Sweden
    • University of Missouri
      • Department of Internal Medicine
      Columbia, Missouri, United States
  • 2012–2013
    • University of Glasgow
      • • BHF Glasgow Cardiovascular Research Centre
      • • Institute of Cardiovascular and Medical Sciences
      Glasgow, SCT, United Kingdom
    • Università degli Studi di Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 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
    • Cardiovascular Research Foundation
      New York City, New York, United States
    • Fakultní nemocnice Královské Vinohrady
      Praha, Praha, Czech Republic
  • 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