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  • 1
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    Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-11-04)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-11-04)
    Abstract: Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even observed a slight mean linear increase of 4.5 ml/m per year during childhood and adolescence for the overall cohort. Patients with two null PKHD1 variants had larger first documented haeTKV values than children with missense variants (median (IQR) haeTKV 793 (450–1098) ml/m in Null/null, 403 (260–538) ml/m in Null/mis, 230 (169–357) ml/m in Mis/mis). In the overall cohort, estimated glomerular filtration rate decreases with increasing haeTKV (median (IQR) haeTKV 210 (150–267) ml/m in CKD stage 1, 472 (266–880) ml/m in stage 5 without kidney replacement therapy). Strikingly, there is a clear correlation between haeTKV in the first eighteen months of life and kidney survival in childhood and adolescence with ten-year kidney survival rates ranging from 20% in patients of the highest to 94% in the lowest quartile. Early childhood haeTKV may become an easily obtainable prognostic marker of kidney disease in ARPKD, e.g. for the identification of patients for clinical studies.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-00523-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 2
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    Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis
    eLife Sciences Publications, Ltd ; 2021
    In:  eLife Vol. 10 ( 2021-05-11)
    Details
    In: eLife, eLife Sciences Publications, Ltd, Vol. 10 ( 2021-05-11)
    Abstract: Heart attacks are caused by a blockage in arteries that supply oxygen to the heart. This often happens when fatty deposits (or ‘plaques’) that line blood vessels break off and create a clot. To identify individuals most at risk of this occurring, physicians currently use symptoms, family history, blood tests, imaging and surgical procedures. But better methods are needed. Imaging blockages in the arteries of individuals who died from heart attacks highlighted certain plaque characteristics that increase the risk of a rupture. Further understanding the forces that lead to these fatty deposits breaking off may help scientists to develop improved heart attack prediction methods. Using patient-specific computer simulations, Milzi et al. show it is possible to predict where plaques are most likely to rupture in an individual, based on biomechanical stresses on the deposits in the artery. The models also showed how forces on the external layers of the plaque played a pivotal role in breakages. More research is needed to confirm the results of this study and to develop automated ways for measuring the stress exerted on plaques in the arteries. If that research is successful, biomechanical analyses of artery plaques in routine patient assessments may one day allow physicians to predict heart attacks and provide life-saving preventive care.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    URL: Article
    DOI: 10.7554/eLife.64020
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2021
    detail.hit.zdb_id: 2687154-3
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  • 3
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    Intrinsic calcification angle: a novel feature of the vulnerable coronary plaque in patients with type 2 diabetes: an optical coherence tomography study
    Springer Science and Business Media LLC ; 2019
    In:  Cardiovascular Diabetology Vol. 18, No. 1 ( 2019-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2019-12)
    Abstract: Coronary calcification is associated with high risk for cardiovascular events. However, its impact on plaque vulnerability is incompletely understood. In the present study we defined the intrinsic calcification angle (ICA) as the angle externally projected by a vascular calcification and analyzed its role as novel feature of coronary plaque vulnerability in patients with type 2 diabetes. Methods Optical coherence tomography was used to determine ICA in 219 calcifications from 56 patients with stable coronary artery disease (CAD) and 143 calcifications from 36 patients with acute coronary syndrome (ACS). We then used finite elements analysis to gain mechanistic insight into the effects of ICA. Results Minimal (139.8 ± 32.8° vs. 165.6 ± 21.6°, p  〈  0.001) and mean ICA (164.1 ± 14.3° vs. 176.0 ± 8.4°, p  〈  0.001) were lower in ACS vs. stable CAD patients. Mean ICA predicted ACS with very good diagnostic efficiency (AUC = 0.840, 95% CI 0.797–0.882, p  〈  0.001, optimal cut-off 175.9°); younger age (OR 0.95 per year, 95% CI 0.92–0.98, p = 0.002), male sex (OR 2.18, 95% CI 1.41–3.38, p  〈  0.001), lower HDL-cholesterol (OR 0.82 per 10 mg/dl, 95% CI 0.68–0.98, p = 0.029) and ACS (OR 14.71, 95% CI 8.47–25.64, p  〈  0.001) were determinants of ICA  〈  175.9°. A lower ICA predicted ACS (OR for 10°-variation 0.25, 95% CI 0.13–0.52, p  〈  0.001) independently from fibrous cap thickness, presence of macrophages or extension of lipid core. In finite elements analysis we confirmed that lower ICA causes increased stress on a lesion’s fibrous cap; this effect was potentiated in more superficial calcifications and adds to the destabilizing role of smaller calcifications. Conclusion Our clinical and mechanistic data for the first time identify ICA as a novel feature of coronary plaque vulnerability.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/s12933-019-0926-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2093769-6
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  • 4
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    Prognostic irrelevance of plaque vulnerability following plaque sealing in high-risk patients with type 2 diabetes: an optical coherence tomography study
    Springer Science and Business Media LLC ; 2020
    In:  Cardiovascular Diabetology Vol. 19, No. 1 ( 2020-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2020-12)
    Abstract: Type 2 diabetes mellitus (T2DM) is associated with an increased cardiovascular risk related at least in part to a more vulnerable plaque phenotype. However, patients with T2DM exhibit also an increased risk following percutaneous coronary intervention (PCI). It is unknown if plaque vulnerability of a treated lesion influences cardiovascular outcomes in patients with T2DM. In this study, we aimed to assess the association of plaque morphology as determined by optical coherence tomography (OCT) with cardiovascular outcome following PCI in high-risk patients with T2DM. Methods 81 patients with T2DM and OCT-guided PCI were recruited. Pre-interventional OCT and systematic follow-up of median 66.0 (IQR = 8.0) months were performed. Results During follow-up, 24 patients (29.6%) died. The clinical parameters age (HR 1.16 per year, 95% CI 1.07–1.26, p  〈  0.001), diabetic polyneuropathy (HR 3.58, 95% CI 1.44–8.93, p = 0.006) and insulin therapy (HR 3.25, 95% CI 1.21–8.70, p = 0.019) predicted mortality in T2DM patients independently. Among OCT parameters only calcium-volume-index (HR 1.71 per 1000°*mm, 95% CI 1.21–2.41, p = 0.002) and lesion length (HR 1.93 per 10 mm, 95% CI 1.02–3.67, p = 0.044) as parameters describing atherosclerosis extent were significant independent predictors of mortality. However, classical features of plaque vulnerability, such as thickness of the fibrous cap, the extent of the necrotic lipid core and the presence of macrophages had no significant predictive value (all p = ns). Conclusion Clinical parameters including those describing diabetes severity as well as OCT-parameters characterizing atherosclerotic extent but not classical features of plaque vulnerability predict mortality in T2DM patients following PCI. These data suggest that PCI may provide effective plaque sealing resulting in limited importance of local target lesion vulnerability for future cardiovascular events in high-risk patients with T2DM.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/s12933-020-01168-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2093769-6
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  • 5
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    Coronary microvascular dysfunction as assessed by angiography-derived index of microvascular resistance co-localizes with and may explain the presence of ischemia in stress-cardiac magnetic resonance imaging in the absence of coronary artery disease
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-11-24)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-24)
    Abstract: Ischemia with no obstructive coronary disease (INOCA) is a frequent phenomenon in the cath lab. A possible cause is coronary microvascular dysfunction (CMD), which may be assessed by invasive testing with possible complications; therefore, less invasive approaches have emerged, such as the angiography-derived index of microvascular resistance (aIMR). The aim of our study was to investigate the association of single-vessel aIMR as a measure of CMD with areas of INOCA in stress testing. Methods We measured aIMR in 286 vessels from 102 patients undergoing both stress cMRI and coronary angiography. Groups were (a) INOCA group (93 vessels, 32 patients); (b) coronary artery disease (CAD) control group (116 vessels, 42 patients) with ischemia due to relevant stenosis; and (c) control group (77 vessels, 28 patients) without ischemia or relevant stenosis. Results INOCA patients presented higher mean aIMR (28.3 ± 5.7) compared to both CAD patients (17.4 ± 5.7, p & lt; 0.001) and controls (22.1 ± 5.9, p & lt; 0.001). Furthermore, in INOCA patients aIMR was significantly increased (33.0 ± 8.1 vs. 25.8 ± 6.3, p = 0.021) in vessels with vs. without ischemia. Single vessel aIMR presented a very good diagnostic efficiency in detecting INOCA [AUC 0.865 (0.804–0.925), optimal cut-off 27.1, p & lt; 0.001]. Conclusion CMD, as assessed by 3-vessel aIMR, co-localizes with and may explain the presence of ischemia in stress-cMRI in INOCA.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.1060764
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
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    Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has no impact on calcification morphology: an intracoronary optical coherence tomography study
    Springer Science and Business Media LLC ; 2017
    In:  Cardiovascular Diabetology Vol. 16, No. 1 ( 2017-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/s12933-017-0635-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2093769-6
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  • 7
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    Quantitative Flow Ratio Is Associated with Extent and Severity of Ischemia in Non-Culprit Lesions of Patients with Myocardial Infarction
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 19 ( 2021-09-30), p. 4535-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 19 ( 2021-09-30), p. 4535-
    Abstract: Quantitative flow ratio (QFR) is a novel method to assess the relevance of coronary stenoses based only on angiographic projections. We could previously show that QFR is able to predict the hemodynamic relevance of non-culprit lesions in patients with myocardial infarction. However, it is still unclear whether QFR is also associated with the extent and severity of ischemia, which can effectively be assessed with imaging modalities such as cardiac magnetic resonance (CMR). Thus, our aim was to evaluate the associations of QFR with both extent and severity of ischemia. We retrospectively determined QFR in 182 non-culprit coronary lesions from 145 patients with previous myocardial infarction, and compared it with parameters assessing extent and severity of myocardial ischemia in staged CMR. Whereas ischemic burden in lesions with QFR 〉 0.80 was low (1.3 ± 5.5% in lesions with QFR ≥ 0.90; 1.8 ± 7.3% in lesions with QFR 0.81–0.89), there was a significant increase in ischemic burden in lesions with QFR ≤ 0.80 (16.6 ± 15.6%; p 〈 0.001 for QFR ≥ 0.90 vs. QFR ≤ 0.80). These data could be confirmed by other parameters assessing extent of ischemia. In addition, QFR was also associated with severity of ischemia, assessed by the relative signal intensity of ischemic areas. Finally, QFR predicts a clinically relevant ischemic burden ≥ 10% with good diagnostic accuracy (AUC 0.779, 95%-CI: 0.666–0.892, p 〈 0.001). QFR may be a feasible tool to identify not only the presence, but also extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10194535
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells
    Oxford University Press (OUP) ; 2022
    In:  Cardiovascular Research Vol. 118, No. 9 ( 2022-07-20), p. 2196-2210
    Details
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 118, No. 9 ( 2022-07-20), p. 2196-2210
    Abstract: Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms. Methods and results We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed tomography (µCT) scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; P  & lt; 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine-induced human primary VSMC calcification, and increased osteogenic gene expression (Runx2, Osx, BSP, and OPN) and extracellular vesicle (EV) secretion. The pro-calcifying effects of nicotine were mediated by Ca2+-dependent Nox5. SiRNA knock-down of Nox5 inhibited nicotine-induced EV release and calcification. Moreover, pre-treatment of hVSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification. Using nicotinic acetylcholine receptor (nAChR) blockers α-bungarotoxin and hexamethonium bromide, we found that the effects of nicotine on intracellular Ca2+ and oxidative stress were mediated by α7 and α3 nAChR. Finally, we showed that Nox5 expression was higher in carotid arteries of smokers and correlated with calcification levels in these vessels. Conclusion In this study, we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    URL: Article
    DOI: 10.1093/cvr/cvab244
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1499917-1
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  • 9
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    Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT
    Public Library of Science (PLoS) ; 2018
    In:  PLOS ONE Vol. 13, No. 10 ( 2018-10-24), p. e0205984-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 13, No. 10 ( 2018-10-24), p. e0205984-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
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    URL: Article
    DOI: 10.1371/journal.pone.0205984
    DOI: 10.1371/journal.pone.0205984.g001
    DOI: 10.1371/journal.pone.0205984.g002
    DOI: 10.1371/journal.pone.0205984.g003
    DOI: 10.1371/journal.pone.0205984.t001
    DOI: 10.1371/journal.pone.0205984.t002
    DOI: 10.1371/journal.pone.0205984.t003
    DOI: 10.1371/journal.pone.0205984.t004
    DOI: 10.1371/journal.pone.0205984.t005
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2018
    detail.hit.zdb_id: 2267670-3
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  • 10
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    Quantitative Flow Ratio Is Related to Intraluminal Coronary Stenosis Parameters as Assessed with Optical Coherence Tomography
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 9 ( 2021-04-24), p. 1856-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 9 ( 2021-04-24), p. 1856-
    Abstract: Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 ± 0.10. QFR demonstrated a consistent association with FFR (r = 0.834, p 〈 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, r = 0.390, p = 0.015), percent area stenosis (r = 0.412, p 〈 0.001), minimal lumen diameter (MLD, r = 0.395, p 〈 0.001), and percent diameter stenosis (r = 0.400, p 〈 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm2) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR ≤ 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10091856
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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