Heleen M M van Beusekom

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (81)374.7 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Angiotensin‐(1–7) improves cardiac function and remodeling after myocardial infarction (MI). This may involve recruitment of hematopoietic progenitor cells that support angiogenesis. However, angiotensin‐(1–7) is rapidly metabolized in plasma and tissue. The authors investigated in mice the effect of a metabolically stable angiotensin‐(1–7) analogue, cyclic angiotensin‐(1–7), on progenitor cell recruitment and on the heart post MI, when given in the angiogenesis phase of remodeling. Methods and Results Angiogenic progenitor cell recruitment was measured by using flow cytometry 24 and 72 hours after a daily bolus injection of cyclic angiotensin‐(1–7) in healthy C57BL/6 mice. Further, mice underwent MI or sham surgery and subsequently received saline or 2 different doses of cyclic angiotensin‐(1–7) for 3 or 9 weeks. Cyclic angiotensin‐(1–7) increased circulating hematopoietic progenitor cells at 24 hours but not 72 hours. Post MI, cyclic angiotensin‐(1–7) diminished cardiomyocyte hypertrophy and reduced myogenic tone, without altering cardiovascular function or cardiac histology at 9 weeks. Importantly, cyclic angiotensin‐(1–7)–treated mice had reduced cardiac capillary density at 3 weeks after MI but not after 9 weeks. Finally, cyclic angiotensin‐(1–7) decreased tube formation by cultured human umbilical vein endothelial cells. Conclusions Our results suggest that cyclic angiotensin‐(1–7), when given early after MI, recruits progenitor cells but does not lead to improved angiogenesis, most likely because it simultaneously exerts antiangiogenic effect in adult endothelial cells. Apparently, optimal treatment with cyclic angiotensin‐(1–7) depends on the time point of onset of application after MI.
    Journal of American Heart Association. 02/2015;
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    ABSTRACT: Intracoronary Fourier-Domain optical coherence tomography (FD-OCT) enables imaging of the coronary artery within 2-4 seconds, a so far unparalleled speed. Despite such fast data acquisition, cardiac and respiratory motion can cause artefacts due to longitudinal displacement of the catheter within the artery. We studied the influence of longitudinal FD-OCT catheter displacement on serial global lumen and scaffold area measurements in coronary arteries of swine that received PLLA-based bioresorbable scaffolds. In 10 swine, 20 scaffolds (18 × 3.0 mm) were randomly implanted in two epicardial coronary arteries. Serial FD-OCT imaging was performed immediately after implantation (T1) and at 3 (T2) and 6 months (T3) follow-up. Two methods for the selection of OCT cross-sections were compared. Method A did not take into account longitudinal displacement of the FD-OCT catheter. Method B accounted for longitudinal displacement of the FD-OCT catheter. Fifty-one OCT pullbacks of 17 scaffolds were serially analyzed. The measured scaffold length differed between time points, up to one fourth of the total scaffold length, indicating the presence of longitudinal catheter displacement. Between method A and B, low error was demonstrated for mean area measurements. Correlations between measurements were high: R(2) ranged from 0.91 to 0.99 for all mean area measurements at all time points. Considerable longitudinal displacement of the FD-OCT catheter was observed, diminishing the number of truly anatomically matching cross-sections in serial investigations. Global OCT dimensions such as mean lumen and scaffold area were not significantly affected by this displacement. Accurate co-registration of cross-sections, however, is mandatory when specific regions, e.g. jailed side branch ostia, are analyzed.
    The international journal of cardiovascular imaging 05/2014; · 2.15 Impact Factor
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    ABSTRACT: Objective To compare heart specific fatty acid binding protein (hFABP) and high sensitive troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct-size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Background Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in absence of reperfusion. We evaluated the fast marker hFABP in comparison to hsTnI to estimate infarct-size and no-reflow upon reperfused and non-reperfused STEMI in swine. Methods In STEMI (n=4) and STEMI+reperfusion (n=8) induced in swine, serial blood samples were taken for hFABP and hsTnI and compared to triphenyl tetrazolium chloride and thioflavin-S staining for infarct-size and no-reflow at sacrifice. Results hFABP increased faster than hsTnI upon occlusion (82±29 vs. 180±73 min, p<0.05) and increased immediately upon reperfusion while hsTnI release was delayed 16±3 min (p<0.05). Peak hFABP and hsTnI reperfusion values were reached 30±5 and 139±21 min. respectively (p<0.05). Infarct-size (containing 84±0.6% no-reflow) correlated well with area under the curve for hFABP (r&sup2;=0.92) but not hsTnI (r&sup2;=0.53). At 50 and 60 minutes reperfusion, hFABP correlated best with infarct-size (r&sup2;=0.94 and 0.93) and no-reflow (r&sup2;=0.96 and 0.94) and showed high sensitivity for myocardial necrosis (2.3±0.6 and 0.4±0.6 gram) Conclusions hFABP rises faster and correlates better with infarct-size and no-reflow than hsTnI in STEMI+reperfusion when measured early after reperfusion. The highest sensitivity detecting myocardial necrosis, 0.4±0.6 gram at 60 minutes post reperfusion, provides an accurate and early measurement of infarct-size and no-reflow.
    AJP Heart and Circulatory Physiology 07/2013; · 4.01 Impact Factor
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    ABSTRACT: Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 05/2013; 9(1):148-156. · 3.17 Impact Factor
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    ABSTRACT: OBJECTIVES: This study sought to assess the vascular response of overlapping Absorb stents compared with overlapping newer-generation everolimus-eluting metallic platform stents (Xience V [XV]) in a porcine coronary artery model. BACKGROUND: The everolimus-eluting bioresorbable vascular scaffold (Absorb) is a novel approach to treating coronary lesions. A persistent inflammatory response, fibrin deposition, and delayed endothelialization have been reported with overlapping first-generation drug-eluting stents. METHODS: Forty-one overlapping Absorb and overlapping Xience V (XV) devices (3.0 × 12 mm) were implanted in the main coronary arteries of 17 nonatherosclerotic pigs with 10% overstretch. Implanted coronary arteries were evaluated by optical coherence tomography (OCT) at 28 days (Absorb n = 11, XV n = 7) and 90 days (Absorb n = 11, XV n = 8), with immediate histological evaluation following euthanasia at the same time points. One animal from each time point was evaluated with scanning electron microscopy alone. A total of 1,407 cross sections were analyzed by OCT and 148 cross sections analyzed histologically. RESULTS: At 28 days in the overlap, OCT analyses indicated 80.1% of Absorb struts and 99.4% of XV struts to be covered (p < 0.0001), corresponding to histological observations of struts with cellular coverage of 75.4% and 99.6%, respectively (p < 0.001). Uncovered struts were almost exclusively related to the presence of "stacked" Absorb struts, that is, with a direct overlay configuration. At 90 days, overlapping Absorb and overlapping XV struts demonstrated >99% strut coverage by OCT and histology, with no evidence of a significant inflammatory process, and comparable % volume obstructions. CONCLUSIONS: In porcine coronary arteries implanted with overlapping Absorb or overlapping XV struts, strut coverage is delayed at 28 days in overlapping Absorb, dependent on the overlay configuration of the thicker Absorb struts. At 90 days, both overlapping Absorb and overlapping XV have comparable strut coverage. The implications of increased strut thickness may have important clinical and design considerations for bioresorbable platforms.
    JACC. Cardiovascular Interventions 05/2013; 6(5):523-532. · 1.07 Impact Factor
  • The Journal of thoracic and cardiovascular surgery 04/2013; · 3.41 Impact Factor
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    ABSTRACT: Critically evaluating the methodology of the adventitial delivery of stem cells, some specific options should be underlined. Adventitia as the most superficial layer, consisting of connective tissue has to be distinguished of perivascular tissues. By strict definition, an adventitia is the outermost connective tissue covering any organ, or vessel. The "adventitial" delivery of stem cells with a 1mm micro-needle means a delivery to superficial so called pericardial myocardium, perivascular fat tissues, including a risk of perforation and injury of soft tissues. In fact, the mapping of the artery with visualization of the three-layer vessel structure and perivascular tissues as well as pericardial space with the state-of-the-art imaging approaches including IVUS (intravascular ultrasound) or OCT (optical coherence tomography) allows to find an optimal site for injection, prevents any technical complications and improves efficacy. NOGA magnetic navigation system still remains the optimal tool for the stem cell delivery to myocardium with appropriate visualization of necrosis and peri-infarct tissues. Potentially, more advanced imaging provides a chance to deliver infusate to the adventitial layer, which is a gate to the vessel wall for inflammation as well as a source of stem and progenitor cells, and myofibroblasts.
    International journal of cardiology 12/2012; · 6.18 Impact Factor
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    ABSTRACT: Coronary atherosclerosis has a high prevalence and is known as the leading cause of death worldwide. Clinically, coronary atherosclerosis is routinely evaluated by coronary angiography, which provides a luminogram of the coronary artery and allows for recognizing lumen narrowing. However, angiography does not allow for the direct assessment of the disease process within the coronary vessel wall. Today, a number of catheter-based imaging methods can overcome this shortcoming and provide physicians with additional information on specific morphological components of atherosclerotic lesions. This article discusses the abilities of intravascular imaging techniques such as intravascular ultrasound (IVUS), IVUS-VH, iMAP, integrated backscatter-IVUS, intravascular optical coherence tomography, near-infrared spectroscopy and angioscopy, to diagnose coronary atherosclerosis and their potential to guide clinical decision making.
    Minerva cardioangiologica 06/2012; 60(3):305-29. · 0.48 Impact Factor
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    ABSTRACT: Intracoronary imaging with intracoronary ultrasound and coherence tomography is often used in the follow-up of coronary stent implantation. The present case shows an infrequent complication of these procedures, suggesting our continued attention to the selective use of these invasive procedures.
    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 04/2012; 20(5):229-31. · 2.26 Impact Factor
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    ABSTRACT: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.
    Journal of the American College of Cardiology 03/2012; 59(12):1058-72. · 15.34 Impact Factor
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    ABSTRACT: Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced DM pigs on a saturated fat/cholesterol (SFC) diet (SFC + DM) were compared with control pigs on SFC and standard (control) diets. SFC + DM pigs showed DM-associated metabolic alterations and early atherosclerosis development in the aorta. Endothelium-dependent vasodilation to bradykinin (BK), with or without blockade of nitric oxide (NO) synthase, endothelium-independent vasodilation to an exogenous NO-donor (S-nitroso-N-acetylpenicillamine), and vasoconstriction to endothelin (ET)-1 with blockade of receptor subtypes, were assessed in vitro. Small coronary arteries, but not conduit vessels, showed functional alterations including impaired BK-induced vasodilatation due to loss of NO (P < 0.01 vs. SFC and control) and reduced vasoconstriction to ET-1 (P < 0.01 vs. SFC and control), due to a decreased ET(A) receptor dominance. Other vasomotor responses were unaltered. In conclusion, this model demonstrates specific coronary microvascular alterations with regard to NO and ET-1 systems in the process of early atherosclerosis in DM. In particular, the altered ET-1 system correlated with hyperglycemia in atherogenic conditions, emphasizing the importance of this system in DM-associated CAD development.
    AJP Heart and Circulatory Physiology 01/2012; 302(1):H85-94. · 4.01 Impact Factor
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    ABSTRACT: Lipid content is a key factor in vulnerable atherosclerotic plaques that may lead to myocardial infarction. Intravascular photoacoustic (IVPA) imaging is a possible method to identify lipid content in the artery wall. We developed a method to automatically detect lipids in human coronary atherosclerosis using spectroscopic IVPA. In cross-sectional IVPA/intravascular ultrasound (IVUS) scans of fresh ex vivo human coronary arteries, we correlated the photoacoustic spectra to a reference lipid spectrum in the 1200 nm spectral range. Correlation coeffcients above a certain cut-off value indicated similarity between IVPA and reference lipid spectra. Automatically detected lipid areas exhibited good correspondence with the histological lipid stain of the same cross section.
    Ultrasonics Symposium (IUS), 2012 IEEE International; 01/2012
  • EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 12/2011; 7(8):1006-7. · 3.17 Impact Factor
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    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 09/2011; 19(10):442-6. · 2.26 Impact Factor
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    ABSTRACT: To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. The introduction of drug-eluting stents has reduced the need for target lesion revascularization, but their effect on delayed healing, inflammation, and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization by capturing CD34-positive cells (EPC) by the stent surface. The first human clinical trial using coronary EPC capture stents showed stent safety but neointimal thickness (NIT) was not reduced compared to bare metal stents (BMS). To understand these responses we studied the coronary response to the EPC capture stent in swine. The stent, coated with murine antihuman monoclonal CD34 antibodies, was assessed with QCA guided stent implantation in normal swine coronary arteries for early endothelialization at 2 and 5 days, and NIT at 28 and 90 days in comparison to control stents carrying a non-specific murine antibody or to BMS. The main finding was that while the EPC capture stent significantly improved early endothelialization it did not reduce NIT at 28 and 90 days. The EPC capture stent improves early endothelialization in swine but this does not affect neointimal thickness as compared to control stents at 28 and 90 days.
    Catheterization and Cardiovascular Interventions 08/2011; 79(2):231-42. · 2.51 Impact Factor
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    ABSTRACT: Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study. Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R(2) = 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs. Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs.
    Cardiovascular Diabetology 07/2011; 10:64. · 3.71 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Heleen van Beusekom, Patrick W Serruys
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 07/2011; 7(3):291. · 3.17 Impact Factor
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    ABSTRACT: We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25 mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30 MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm. Simultaneous imaging with intravascular ultrasound was performed.
    Optics Letters 03/2011; 36(5):597-9. · 3.39 Impact Factor
  • W J Van Der Giessen, H M M Van Beusekom
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    ABSTRACT: Current drug-eluting stents (DES) perform well compared to bare metal stents. However, long-term rates of major adverse events and in particular repeat revascularization by PCI are still an issue. In this concise review we will discuss the possibilities of biodegradable coatings to improve biocompatibility of DES. Among the various members of the synthetic biodegradable polymer family, polyesters are widely used and attractive for their ease of degradation, with degradation products often being resorbed through general metabolic pathways. A new development is surface functionalization of polyesters to improve endothelialization.
    Minerva cardioangiologica 02/2011; 59(1):31-8. · 0.48 Impact Factor
  • EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 12/2010; 6 Suppl J:J155-60. · 3.17 Impact Factor

Publication Stats

2k Citations
374.70 Total Impact Points


  • 2001–2012
    • Erasmus MC
      • Department of Cardiology
      Rotterdam, South Holland, Netherlands
  • 2011
    • Wageningen University
      Wageningen, Gelderland, Netherlands
  • 1992–2010
    • Erasmus Universiteit Rotterdam
      • • Department of Cardiology
      • • Department of Cardio-Thoracic Surgery
      Rotterdam, South Holland, Netherlands
  • 2009
    • Kocaeli University
      Cocaeli, Kocaeli, Turkey
  • 2008
    • Northern Inyo Hospital
      Bishop, California, United States
  • 2007
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 2002
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands