Publications by authors named "N van Royen"

248 Publications

Features of atherosclerosis in patients with angina and no obstructive coronary artery disease.

EuroIntervention 2022 Jan 27. Epub 2022 Jan 27.

Radboud University Medical Center, Department of Cardiology, Nijmegen, the Netherlands.

Background: An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published.

Aims: This study aims to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm.

Methods: From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups, according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability.

Results: ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] versus 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm.

Conclusions: The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.
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http://dx.doi.org/10.4244/EIJ-D-21-00875DOI Listing
January 2022

Extremity Dysfunction After Large-Bore Radial and Femoral Arterial Access.

J Am Heart Assoc 2022 Jan 13;11(2):e023691. Epub 2022 Jan 13.

Department of Cardiology Isala Heart Center Zwolle the Netherlands.

Background The use of large-bore (LB) arterial access and guiding catheters has been advocated for complex percutaneous coronary intervention. However, the impact of LB transradial access (TRA) and transfemoral access (TFA) on extremity dysfunction is currently unknown. Methods and Results The predefined substudy of the COLOR (Complex Large-Bore Radial PCI) trial aimed to assess upper and lower-extremity dysfunction after LB radial and femoral access. Upper-extremity function was assessed in LB TRA-treated patients by the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and lower-extremity function in LB TFA-treated patients by the Lower Extremity Functional Scale questionnaire. Extremity pain and effect of access site complications and risk factors on extremity dysfunction was also analyzed. There were 343 patients who completed analyzable questionnaires. Overall, upper and lower-extremity function did not decrease over time when LB TRA and TFA were used for complex percutaneous coronary intervention, as represented by the median Quick Disabilities of the Arm, Shoulder, and Hand score (6.8 at baseline and 2.1 at follow-up, higher is worse) and Lower Extremity Functional Scale score (56 at baseline and 58 at follow-up, lower is worse). Clinically relevant extremity dysfunction occurred in 6% after TRA and 9% after TFA. A trend for more pronounced upper-limb dysfunction was present in female patients after LB TRA (=0.05). Lower-extremity pain at discharge was significantly higher in patients with femoral access site complications (=0.02). Conclusions Following LB TRA and TFA, self-reported upper and lower-limb function did not decrease over time in the majority of patients. Clinically relevant limb dysfunction occurs in a small minority of patients regardless of radial or femoral access. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03846752.
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http://dx.doi.org/10.1161/JAHA.121.023691DOI Listing
January 2022

Acetylcholine Rechallenge: A First Step Toward Tailored Treatment in Patients With Coronary Artery Spasm.

JACC Cardiovasc Interv 2022 Jan;15(1):65-75

Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.

Objectives: The present study aimed to assess the feasibility and clinical value of acetylcholine (ACh) rechallenge for the detection of coexisting epicardial and microvascular spasm and to determine the efficacy of nitroglycerin in these spasm endotypes.

Background: The coexistence of epicardial and microvascular spasm is difficult to identify; thus, its frequency is unknown. Nitroglycerin treatment is equally recommended for both epicardial and microvascular coronary spasm despite contradictory data.

Methods: In this multicenter study, 95 patients with coronary spasm were included to undergo ACh rechallenge, which consisted of repeated ACh provocation 3 minutes after intracoronary nitroglycerin administration using the same dose that previously induced spasm.

Results: In total, 95 patients (age 61 ± 12 years, 69% female) were included. Fifty-five patients (58%) had microvascular spasm, and 40 patients (42%) had epicardial spasm during initial ACh provocation. In 48% of patients with epicardial spasm, ACh rechallenge revealed coexisting nitroglycerin-persistent microvascular spasm. Nitroglycerin administration before ACh rechallenge prevented reinducibility of epicardial spasm in all patients with focal spasm and in 80% of patients with diffuse spasm. Microvascular spasm was prevented in only 20% by prior nitroglycerin administration but was attenuated in another 49% of patients.

Conclusions: This study demonstrates a high frequency of epicardial spasm with coexisting nitroglycerin-persistent microvascular spasm. Intracoronary nitroglycerin was very effective in preventing reinducibility of epicardial spasm, whereas it prevented microvascular spasm in only 20% of patients. ACh rechallenge is a novel method that facilitates the detection of coexisting spasm endotypes and may pave the way towards tailored treatment of vasospastic angina.
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http://dx.doi.org/10.1016/j.jcin.2021.10.003DOI Listing
January 2022

Anti-Galectin-2 antibody treatment reduces atherosclerotic plaque size and alters macrophage polarity.

Thromb Haemost 2021 Dec 1. Epub 2021 Dec 1.

Partner Site Munich Heart Alliance, DZHK, Munich, Germany.

Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 blockade in ischaemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Galectin-2 may also affect other macrophage related cardiovascular diseases. This study aims to elucidate the effects of Galectin-2 inhibition in atherosclerosis. ApoE -/- mice were given a high cholesterol diet (HCD) for 12 weeks. After six weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama derived anti-Gal2 nanobodies (clones- 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Galectin-2 inhibition reduced the progression of existing atherosclerosis. Atherosclerotic plaque area in the aortic root was decreased, especially so in mice treated with 2C10 nanobodies. This clone reduced atherosclerosis severity as reflected by a decrease in fibrous cap atheromas in addition to decreases in plaque size. The number of plaque resident macrophages was unchanged, however, there was a significant increase in the fraction of CD206+ macrophages. 2C10 treatment also increased plaque α-smooth muscle content, and Gal-2 may have a role in modulating the inflammatory status of smooth muscle cells. Remarkably, both treatments reduced serum cholesterol concentrations including reductions in VLDL, LDL, and HDL whilst triglyceride concentrations were unchanged. Prolonged treatment with anti-Gal-2 nanobodies reduced plaque size, slowed plaque progression, and modified the phenotype of plaque macrophages toward an anti-inflammatory profile. These results hold promise for future macrophage modulating therapeutic interventions that promote arteriogenesis and reduce atherosclerosis.
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http://dx.doi.org/10.1055/a-1711-1055DOI Listing
December 2021

Optical coherence tomography and coronary revascularization: from indication to procedural optimization.

Trends Cardiovasc Med 2021 Oct 30. Epub 2021 Oct 30.

Department of Cardiology, Radboudumc, Nijmegen, the Netherlands. Electronic address:

Angiography alone is the most commonly used imaging modality for guidance of percutaneous coronary interventions. Angiography is limited, however, by several factors, including that it only portrays a low resolution, two-dimensional outline of the lumen and does not inform on plaque composition and functional stenosis severity. Optical coherence tomography (OCT) is an intracoronary imaging technique that has superior spatial resolution compared to all other imaging modalities. High-resolution imaging of the vascular wall enables precise measurement of vessel wall and luminal dimensions, more accurately informing about the anatomic severity of epicardial stenoses, and also provides input for computational models to assess functional severity. The very high-resolution images also permit plaque characterization that may be informative for prognostication. Moreover, periprocedural imaging provides valuable information to guide lesion preparation, stent implantation and to evaluate acute stent complications for which iterative treatment might reduce the occurrence of major adverse stent events. As such, OCT represent a potential future all-in-one tool that provides the data necessary to establish the indications, procedural planning and optimization, and final evaluation of percutaneous coronary revascularization.
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http://dx.doi.org/10.1016/j.tcm.2021.10.009DOI Listing
October 2021
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