Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk ...atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification.
Aortic stenosis is a common condition associated with major morbidity, mortality, and health-care costs. Nevertheless, we currently lack any effective medical therapies that can treat or prevent ...disease development or progression. Modern advances in echocardiography and CT have helped improve the assessment of aortic stenosis severity and monitoring of disease progression, whereas cardiac MRI informs on myocardial health and the development of fibrosis. In a series of recent studies,
F-NaF PET/CT has been shown to assess valvular disease activity and progression, providing mechanistic insights that can inform potential novel therapeutic approaches. This review will examine the latest advances in the imaging of aortic stenosis and bioprosthetic valve degeneration and explore how these techniques can assist patient management and potentially accelerate novel therapeutic developments.
Introduction: In aortic stenosis (AS), there are clear sex differences in clinical presentation, left ventricular (LV) response to pressure overload, and pathophysiology of valvular calcification. ...These differences may affect outcome following valve intervention.
Area covered: This review aims to discuss sex differences in clinical presentation, pathophysiology of aortic valve calcification, LV remodeling in view of historic and recent echocardiographic and cardiac magnetic resonance imaging studies, and outcome after valve intervention. In addition, it will also provide some brief insights on the exercise physiology in women and men with AS.
Expert commentary: Women at presentation are often older, have higher prevalence of hypertension and diastolic dysfunction, while men are younger, and more often have a bicuspid aortic valve and higher atherosclerotic disease burden. Men have more valve calcification than women for a given severity of AS and develop different patterns of LV remodeling and myocardial fibrosis. Although women tend to walk shorter on treadmill and achieve lower metabolic equivalents, they achieve similar peak heart rates and blood pressure, and the frequency of revealed symptoms during exercise test is comparable in both sexes. Men are more likely to undergo a surgical AVR with better outcome, while women have generally better outcome after TAVI.
Calcific aortic valve stenosis is the commonest form of heart valve disease in high-income countries and set to become a major health care burden. Currently, there are no medical therapies that have ...proved to slow down or halt disease progression. The only available treatment is aortic valve replacement, of which the optimal timing is unknown and to which not all patients are suited. This review discusses the pathophysiology of aortic stenosis, how noninvasive imaging techniques have improved our understanding of the underlying biology, and how these emerging insights might translate into potential novel treatments targeting oxidized lipids, fibrosis, and calcification.
Calcific aortic valve stenosis (CAVS) is common in the ageing population and set to become an increasing economic and health burden. Once present, it inevitably progresses and has a poor prognosis in ...symptomatic patients. No medical therapies are proven to be effective in holding or reducing disease progression. Therefore, aortic valve replacement remains the only available treatment option. Improved knowledge of the mechanisms underlying disease progression has provided us with insights that CAVS is not a passive disease. Rather, CAVS is regulated by numerous mechanisms with a key role for calcification. Aortic valve calcification (AVC) is actively regulated involving cellular and humoral factors that may offer targets for diagnosis and intervention. The discovery that the vitamin K-dependent proteins are involved in the inhibition of AVC has boosted our mechanistic understanding of this process and has opened up novel avenues in disease exploration. This review discusses processes involved in CAVS progression, with an emphasis on recent insights into calcification, methods for imaging calcification activity, and potential therapeutic options.
Coronary computed tomography angiography (CTA) has shown great technological improvements over the last 2 decades. High accuracy of CTA in detecting significant coronary stenosis has promoted CTA as ...a substitute for conventional invasive coronary angiography in patients with suspected coronary artery disease. In patients with coronary stenosis, CTA-derived physiological assessment is surrogate for intracoronary pressure and velocity wires, and renders possible decision-making about revascularization solely based on computed tomography. Computed tomography coronary anatomy with functionality assessment could potentially become a first line in diagnosis. Noninvasive imaging assessment of plaque burden and morphology is becoming a valuable substitute for intravascular imaging. Recently, wall shear stress and perivascular inflammation have been introduced. These assessments could support risk management for both primary and secondary cardiovascular prevention. Anatomy, functionality, and plaque composition by CTA tend to replace invasive assessment. Complete CTA assessment could provide a 1-stop-shop for diagnosis, risk management, and decision-making on treatment.
With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional ...innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using
18
FFDG, but 4Is PET radiopharmaceuticals beyond
18
FFDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.
Abstract
Calcific aortic valve stenosis (CAVS) is common in the ageing population and set to become an increasing economic and health burden. Once present, it inevitably progresses and has a poor ...prognosis in symptomatic patients. No medical therapies are proven to be effective in holding or reducing disease progression. Therefore, aortic valve replacement remains the only available treatment option. Improved knowledge of the mechanisms underlying disease progression has provided us with insights that CAVS is not a passive disease. Rather, CAVS is regulated by numerous mechanisms with a key role for calcification. Aortic valve calcification (AVC) is actively regulated involving cellular and humoral factors that may offer targets for diagnosis and intervention. The discovery that the vitamin K-dependent proteins are involved in the inhibition of AVC has boosted our mechanistic understanding of this process and has opened up novel avenues in disease exploration. This review discusses processes involved in CAVS progression, with an emphasis on recent insights into calcification, methods for imaging calcification activity, and potential therapeutic options.
CMR was undertaken in 143 consecutive patients: age 68 ± 14 years, 97 (68%) male, aortic valve area 1.0 ± 0.3 cm2, left ventricular ejection fraction (LVEF) 58 ± 19%, and 81 (57%) with known coronary ...artery disease (4). References 1 M.R. Dweck, N.A. Boon, D.E. Newby, Calcific aortic stenosis: a disease of the valve and the myocardium, J Am Coll Cardiol, Vol. 60, 2012, 1854-1863 2 S. Hein, E. Arnon, S. Kostin, Progression from...
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