Topics

Assessment of Risk in Thoracic Aortopathy Using 18F-Sodium Fluoride

2019-09-13 02:15:38 | BioPortfolio

Summary

Patients with bicuspid aortic valve-related aortopathy are at increased risk of aortic dilatation, dissection and rupture. Currently, risk stratification is largely based on aortic diameter measurements, with those deemed high risk referred for aortic replacement surgery. This approach is imperfect, and potentially exposes many patients to unnecessary high-risk aortic surgery, or fails to identify those at risk of dissection or rupture with smaller diameters. In patients with abdominal aortic aneurysms, the investigators recently demonstrated that uptake of 18F-sodium fluoride predicts disease progression and clinical events independent of aneurysm diameter and standard clinical risk factors. Based on the investigators preliminary data, a study was proposed to look at 18F-sodium fluoride uptake in patients with bicuspid aortic valve-related aortopathy. The proposed study will shed light on the underlying pathological processes involved in aortic complications of this disease as well as potentially providing an important risk marker to predict disease progression and guide the need for major aortic surgery.

Description

Bicuspid aortic valve, along with other congenital conditions affecting the aortic wall, has been associated with elastic fibre loss, decrease in size of elastic lamellae, increased collagen deposition and smooth muscle loss compared to healthy controls on both light microscopy and electron microscopy. Further, analysis of site specific regions of the ascending aorta using biopsy specimens demonstrated significant differences in the apoptosis rate and survival of smooth muscle cells favouring the lesser curvature over the greater curvature of the aorta (the area of greater wall shear stress).

Studies to date suggest vessel wall microcalcification (lesions<50μm) is a dynamic marker of this vessel wall pathology: the end-product of a pathological process involving vessel wall inflammation, apoptosis and necrosis of medial smooth muscle cells and subsequent elastic fibre degradation. Granular medial calcinosis, the deposition of microcalcification in the medial layer of resected aortic tissue, has been recognised as a significant feature of bicuspid aortic valve-related aortopathy when compared to aortic samples taken from patients with tricuspid valves.

Recent histological analysis of human and murine Marfan aortas demonstrated elastin breaks co- localising with areas of microcalcification in aortic media. Further, the areas of elastin break were significantly correlated to decreased distensibility and increased aortic diameter. Finally, the group demonstrated an elastin receptor complex-ERK1/2-ALP-mediated mechanism for increased microcalcification deposition. Although focused on Marfan syndrome, these results are relevant to bicuspid aortic valve-related aortopathy as they suggest microcalcification is associated with elastic fibre breakdown, a proposed mechanism of bicuspid aortic valve aneurysm formation at areas of high wall shear stress. The ability to demonstrate and quantify aortic microcalcification, both ex vivo and non-invasively in vivo in patients with bicuspid aortic valve-related aortopathy would be important step in improving our knowledge of the pathological process underpinning this condition.

Positron emission tomography (PET) utilises a radiotracer which provides functional information on tissues at the cellular or molecular level. Because of its limited spatial resolution, PET images are combined with computed tomography (CT) or magnetic resonance imaging (MRI) so that the functional PET images can be co-registered with the detailed anatomical and structural images afforded by CT or MRI. While CT or MRI alone has been utilised in a wide range of cardiovascular diseases and can identify larger areas of macrocalcification (>200 μm), PET/CT using 18F-sodium fluoride has been used to identify vessel wall microcalcification (calcific lesions <50 μm) that is not detectable on CT or MRI. 18F-Sodium fluoride has been extensively validated as a radiotracer of microcalcification utilising electron microscopy, immunohistochemical analysis, pharmacodynamic concentration-response curves, and ex vivo and in vivo micro-PET/CT on vessel wall sections. 18F-Sodium fluoride uptake is mediated through exchange of fluoride ions with hydroxyl groups of hydroxyapatite, the major constituent of vessel wall calcification. Positron emission tomography using 18F-sodium fluoride has demonstrated significant promise as identifying active vessel wall pathology in a number of cardiovascular diseases including carotid, coronary, aortic valve, and abdominal aortic aneurysm disease. The use of 18F-sodium fluoride PET imaging in thoracic aortic aneurysms is novel.

There is a correlation between areas of high wall stress and intimal tear location location. Further, aneurysmal aortic tissue has been demonstrated to have reduced delamination strength in both longitudinal and circumferential dimensions: evidence for an involvement of haemodynamic effects on precipitating dissection. Time resolved 3D blood flow captured on MRI, also known as 4D-flow MRI, is an evolving research tool which non-invasively captures patient-specific regionalised blood flow and velocity, allowing calculation of aortic wall sheer stress, and has been used to study bicuspid aortic valve-related aortopathy. A study pairing pre-operative 4D-flow MRI and post-operative biopsies of aortic tissue have demonstrated a decrease in elastin at sites of high aortic wall stress, suggesting a relationship between haemodynamics and the structural composition of the aneurysmal aortic wall. The ability to demonstrate a pathological process associated with aneurysmal weakness could be an important step to better identifying high risk lesions.

Study Design

Conditions

Bicuspid Aortic Valve

Intervention

clinical evaluation, blood markers, pulse wave analysis, 18F sodium fluoride PET/CT and PET/MRI, Repeat 18F sodium fluoride PET/MRI

Location

University of Edinburgh
Edinburgh
United Kingdom
EH16 4SB

Status

Recruiting

Source

University of Edinburgh

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-09-13T02:15:38-0400

Clinical Trials [3881 Associated Clinical Trials listed on BioPortfolio]

Non-invasive Validation of Non-invasive Central Blood Pressure Measurements Using Oscillometric Pulse Wave Analysis

There is growing evidence that central blood pressure is a better predictor of hypertensive end-organ damage and cardiovascular outcome than routine brachial readings. The investigators a...

Validation Study of Pulse Wave Velocity and Augmentation Index in Atrial Fibrillation

This study aims to evaluate the reliability of measurements of arterial stiffness (pulse wave velocity (PWV), pulse wave contour analysis (PWA), central augmentation index (AIx) and pulse ...

Invasive Validation of Non-invasive Central Blood Pressure Measurements Using Oscillometric Pulse Wave Analysis

There is growing evidence that central blood pressure is a better predictor of hypertensive end-organ damage and cardiovascular outcome than routine brachial readings. We aimed to evaluat...

The Influence of Vitamin D on Mineral Metabolism, Blood Pressure and Pulse Wave Analysis in Healthy Individuals

A randomized placebo controlled trial evaluating the effect of the recently recommended high doses of cholecalciferol (3000 IU/day) on mineral metabolism, blood pressure and pulse wave ana...

International Registry for Ambulatory Blood Pressure and Arterial Stiffness Telemonitoring

This Registry is an investigator-initiated, international, multicenter, observational, prospective study aiming at: i) evaluating non-invasive 24-h ambulatory blood pressure and arterial s...

PubMed Articles [46889 Associated PubMed Articles listed on BioPortfolio]

Association of Estimated Pulse Wave Velocity With Survival: A Secondary Analysis of SPRINT.

Aortic stiffness, as assessed by carotid-femoral pulse wave velocity, is an independent predictor of future events in individuals with hypertension. Recent data suggest a predictive role of estimated ...

Wearable Millimeter-Wave Device for Contactless Measurement of Arterial Pulses.

Wearable monitors for measuring vital signs such as blood pressure will greatly impact the medical field. This work presents a millimeter-wave, radar-based system for performing accurate measurements ...

Relationship between blood lipid and arterial stiffness in hypertension.

To explore the relationship between blood lipids and pulse wave velocity (PWV).

Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men.

The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atheroscler...

Weak within-individual association of blood pressure and pulse wave velocity in hemodialysis is related to adverse outcomes.

Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies i...

Medical and Biotech [MESH] Definitions

Evaluation of the contour of the PULSE waves which vary in different parts of the circulation and depend on physiological as well as pathophysiological conditions of the individual.

Self evaluation of whole blood glucose levels outside the clinical laboratory. A digital or battery-operated reflectance meter may be used. It has wide application in controlling unstable insulin-dependent diabetes.

An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.

Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.

Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.

More From BioPortfolio on "Assessment of Risk in Thoracic Aortopathy Using 18F-Sodium Fluoride"

Quick Search

Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Congenital Diseases
Congenital conditions are those which are present from birth. They include structural deformities or loss of function in organs such as the <!--LGfEGNT2Lhm-->heart, gut or skeletal system. They can be corrected by <!--LGfEGNT2Lhm-->surgery, m...


Searches Linking to this Trial