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  • 1
    In: IJC Heart & Vasculature, Elsevier BV, Vol. 43 ( 2022-12), p. 101128-
    Type of Medium: Online Resource
    ISSN: 2352-9067
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2818464-6
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  • 2
    In: Clinical Genetics, Wiley, Vol. 102, No. 5 ( 2022-11), p. 404-413
    Abstract: Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation 〉 40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort ( n  = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population ( p   〈  0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population ( p  = 0.027) or compared with younger MFS patients ( p  = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain ( p  = 0.022) and symptoms of depression with unemployment ( p  = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms.
    Type of Medium: Online Resource
    ISSN: 0009-9163 , 1399-0004
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2004581-5
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  • 3
    In: Clinical Epigenetics, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process. Methods The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed. Results We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p   〈  10 –8 or p   〈  10 –6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before. Conclusion This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.
    Type of Medium: Online Resource
    ISSN: 1868-7075 , 1868-7083
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2553921-8
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  • 4
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. 43 ( 2020-11-14), p. 4181-4187
    Abstract: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. Methods and results In the original COMPARE study (inclusion 2008–2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26–43) years, control 41 (IQR 30–52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. Conclusion These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2001908-7
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  • 5
    In: Open Heart, BMJ, Vol. 8, No. 2 ( 2021-10), p. e001775-
    Abstract: Patients with Marfan syndrome (MFS) are prone to develop aortic aneurysms due to fragmentation of elastic fibres, resulting in reduced distensibility of the aorta. Reduced distensibility was previously shown to predict progressive descending aorta dilatation. Here, we investigated longitudinal changes in distensibility, as a potential predictor of aortic events. Methods This retrospective study included all patients with MFS with at least four cardiac magnetic resonance examinations performed between 1996 and 2012. Aortic distensibility was assessed, in the ascending (level 1), proximal descending (level 2) and distal descending (level 3) aorta. Changes in distensibility were studied using linear mixed-effects regression models. Results In total, 35 patients with MFS (age at inclusion 28 (IQR 23–32) years, 54% men) were included. Mean aortic distensibility was already low (between 2.9×10 –3 /mm Hg/year and 6.4×10 –3 /mm Hg/year) at all levels at baseline, and significantly decreased over time at levels 2 and 3 (respectively, p=0.012 and p=0.002). The rate of distensibility loss per year (×10 -3 /mm Hg/year) was 0.01, 0.03 and 0.06×10 –3 /mm Hg at levels 1, 2 and 3, respectively. At inclusion, men exhibited very low distensibility, whereas women showed moderately reduced distensibility, gradually decreasing with age. Aortic dilatation rate at level 2 was associated with reduced aortic distensibility. However, we could not demonstrate a direct correlation between distensibility and clinical events during a follow-up of 22 years. Conclusion Patients with MFS display reduced aortic distensibility already at an early age, inversely relating to aortic dilatation rate. However, in this selected patient group, distensibility seems less suitable as an individual predictor of aortic events.
    Type of Medium: Online Resource
    ISSN: 2053-3624
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2747269-3
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  • 6
    In: Catheterization and Cardiovascular Interventions, Wiley, Vol. 93, No. 2 ( 2019-02)
    Abstract: Available data indicate mixed outcomes after using retrograde techniques for chronic total occlusion(CTO) recanalization, with generally higher need for repeat revascularization. Aim of this study is to analyze the angiographic and clinical outcome of patients treated with retrograde techniques in the PRISON‐IV trial. Methods and Results This is a post‐hoc sub‐analysis from the randomized PRISON‐IV trial. Briefly, 330 patients with a successfully recanalized CTO lesion were randomized 1:1 to receive either hybrid‐SES or EES. The hybrid‐SES failed to reach the non‐inferiority primary endpoint of in‐segment late lumen loss at 9‐month angiography follow‐up. In the present analysis, we divided the population according to the first technical approach, namely antegrade ( n  = 285) or retrograde approach ( n  = 45). Demographic characteristics were similar between the two groups, while angiographic features disclosed higher CTO lesion complexity in the group treated with retrograde techniques (J‐CTO score: 1.8 ± 1.1 vs 2.6 ± 1.1, respectively, P   〈  0.001), with longer occlusions (17.6 ± 10 mm vs 28.8 ± 18.7 mm, P   〈  0.001) and longer stented segment (48.9 ± 24.4 mm vs 73.1 ± 33.2 mm, P   〈  0.001). Quantitative coronary analysis disclosed similar results at follow‐up angiography, with a non‐significantly higher in‐stent late‐lumen loss in the retrograde group (0.08 ± 0.52 mm vs 0.18 ± 0.56 mm, P  = 0.32). Clinical follow‐up at 12‐months showed similar outcome, with a non‐significantly higher target‐lesions revascularization rate in the retrograde group (6% vs 11.1% respectively, P  = 0.2). Significant improvements in angina functional class were observed in both groups. Conclusions The present analysis supports the benefits of retrograde techniques in CTO revascularization, with non‐significant differences in angiographic and clinical outcomes at late follow‐up.
    Type of Medium: Online Resource
    ISSN: 1522-1946 , 1522-726X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2001555-0
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