Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study
Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel related disorders including vascular cognitive impairment (VCI) due to cerebra...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2023-01-01
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| Series: | Cerebrovascular Diseases Extra |
| Online Access: | https://www.karger.com/Article/FullText/529067 |
| _version_ | 1811168104063959040 |
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| author | Maud van Dinther Jonathan Bennett George D. Thornton Paulien H.M. Voorter Ana Ezponda Casajús Alun Hughes Gabriella Captur Robert J. Holtackers Julie Staals Walter H. Backes Gorka Bastarika Elizabeth A.V. Jones Arantxa González Robert van Oostenbrugge Thomas Alexander Treibel |
| author_facet | Maud van Dinther Jonathan Bennett George D. Thornton Paulien H.M. Voorter Ana Ezponda Casajús Alun Hughes Gabriella Captur Robert J. Holtackers Julie Staals Walter H. Backes Gorka Bastarika Elizabeth A.V. Jones Arantxa González Robert van Oostenbrugge Thomas Alexander Treibel |
| author_sort | Maud van Dinther |
| collection | DOAJ |
| description | Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these co-morbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity.
Methods/design: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment.
Discussion: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow pre-clinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets. |
| first_indexed | 2024-04-10T16:20:26Z |
| format | Article |
| id | doaj.art-94670632d4474dde86a8d1e0579a34f7 |
| institution | Directory Open Access Journal |
| issn | 1664-5456 |
| language | English |
| last_indexed | 2024-04-10T16:20:26Z |
| publishDate | 2023-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Cerebrovascular Diseases Extra |
| spelling | doaj.art-94670632d4474dde86a8d1e0579a34f72023-02-09T15:14:03ZengKarger PublishersCerebrovascular Diseases Extra1664-54562023-01-011110.1159/000529067529067Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational studyMaud van Dintherhttps://orcid.org/0000-0001-7349-4783Jonathan Bennetthttps://orcid.org/0000-0002-8810-5936George D. Thorntonhttps://orcid.org/0000-0003-3289-2413Paulien H.M. Voorterhttps://orcid.org/0000-0002-2724-4502Ana Ezponda CasajúsAlun HughesGabriella CapturRobert J. Holtackershttps://orcid.org/0000-0003-1809-313XJulie StaalsWalter H. BackesGorka Bastarikahttps://orcid.org/0000-0001-9493-6907Elizabeth A.V. Joneshttps://orcid.org/0000-0002-2006-7064Arantxa GonzálezRobert van OostenbruggeThomas Alexander TreibelIntroduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these co-morbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity. Methods/design: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. Discussion: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow pre-clinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.https://www.karger.com/Article/FullText/529067 |
| spellingShingle | Maud van Dinther Jonathan Bennett George D. Thornton Paulien H.M. Voorter Ana Ezponda Casajús Alun Hughes Gabriella Captur Robert J. Holtackers Julie Staals Walter H. Backes Gorka Bastarika Elizabeth A.V. Jones Arantxa González Robert van Oostenbrugge Thomas Alexander Treibel Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study Cerebrovascular Diseases Extra |
| title | Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study |
| title_full | Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study |
| title_fullStr | Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study |
| title_full_unstemmed | Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study |
| title_short | Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study |
| title_sort | evaluation of microvascular rarefaction in vascular cognitive impairment and heart failure crucial study protocol for an observational study |
| url | https://www.karger.com/Article/FullText/529067 |
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