Multiple biomarker panel to screen for severe aortic stenosis: results from the CASABLANCA study

Elmariah, Sammy; McCarthy, Cian P.; Ibrahim, Nasrien E.; Furman, Deborah; Mukai, Renata; Magaret, Craig A.; Rhyne, Rhonda F.; Barnes, Grady; Kimmenade, Roland R.J. van; Januzzi, James L.

doi:10.1136/openhrt-2018-000916

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…Whilst individual studies have reported on multiple biomarkers [77,78], this is the first systematic review and meta-analysis to date that assesses the association of multiple biomarkers with mortality in a wider population of patients with AS.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

et al. 2021

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The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95–3.44; p < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45–2.06; p = 0.00001), Troponin (HR 1.65; 95% CI 1.31–2.07; p < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27–2.61; p < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status.

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Section: Discussionmentioning

confidence: 99%

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

et al. 2021

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“…Due to the overlap in mechanisms behind BNP release, it is non-specific for AS in isolation 57 71. As a result, an approach with multiple biomarkers may provide better insight 64 65 72…”

Section: Emerging Assessment Techniquesmentioning

confidence: 99%

Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis

Shah

Lakey

et al. 2023

Open Heart

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Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the condition’s mechanistic underpinning has shifted the paradigm to an active disease process. This advancement from the ‘wear and tear’ model is a result of the growing economic and health burden of AS, particularly within industrialised countries, prompting further research. The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options.There is an unmet clinical need for asymptomatic patient management; no pharmacotherapies are proven to slow progression and intervention timing varies. Novel approaches are developing to address this through: (1) screening with circulating biomarkers; (2) development of drugs to slow disease progression and (3) early valve intervention guided by medical imaging. Existing biomarkers (troponin and brain natriuretic peptide) are non-specific, but cost-effective predictors of ventricular dysfunction. In addition, their integration with cardiovascular MRI can provide accurate risk stratification, aiding aortic valve replacement decision making. Currently, invasive intervention is the only treatment for AS. In comparison, the development of lipoprotein(a) lowering therapies could provide an alternative; slowing progression of CAS, preventing left ventricular dysfunction and reducing reliance on surgical intervention.The landscape of AS management is rapidly evolving. This review outlines current understanding of the pathophysiology of AS, its management and future perspectives for the condition’s assessment and treatment.

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“…Notch may have an important role in aortic valve calcification ( Kostina et al, 2018 ) and the Notch ligand Delta-1 is elevated and associated with mortality in patients with symptomatic aortic stenosis ( Abraityte et al, 2015 ). Elmariah et al suggested that a panel of multiple biomarkers including age, NT-proBNP, vWF, and fetuin-A would be valuable for the identification of high-risk patients with aortic stenosis and for timely valve intervention ( Elmariah et al, 2018 ). MacGrogan et al also suggested that a set of several genes in blood provided a “gene signature” predicting aortic valve calcification ( MacGrogan et al, 2020 ).…”

Section: Biomarkers Of Aortic Valve Calcificationmentioning

confidence: 99%

Models and Techniques to Study Aortic Valve Calcification in Vitro, ex Vivo and in Vivo. An Overview

Bogdanova

Zabirnyk²,

Malashicheva³

et al. 2022

Front. Pharmacol.

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Aortic valve stenosis secondary to aortic valve calcification is the most common valve disease in the Western world. Calcification is a result of pathological proliferation and osteogenic differentiation of resident valve interstitial cells. To develop non-surgical treatments, the molecular and cellular mechanisms of pathological calcification must be revealed. In the current overview, we present methods for evaluation of calcification in different ex vivo, in vitro and in vivo situations including imaging in patients. The latter include echocardiography, scanning with computed tomography and magnetic resonance imaging. Particular emphasis is on translational studies of calcific aortic valve stenosis with a special focus on cell culture using human primary cell cultures. Such models are widely used and suitable for screening of drugs against calcification. Animal models are presented, but there is no animal model that faithfully mimics human calcific aortic valve disease. A model of experimentally induced calcification in whole porcine aortic valve leaflets ex vivo is also included. Finally, miscellaneous methods and aspects of aortic valve calcification, such as, for instance, biomarkers are presented.

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Multiple biomarker panel to screen for severe aortic stenosis: results from the CASABLANCA study

Cited by 8 publications

References 32 publications

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis

Models and Techniques to Study Aortic Valve Calcification in Vitro, ex Vivo and in Vivo. An Overview

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