Dataset Information

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

ABSTRACT: Objective:Severe aortic valve stenosis (AS) develops via insidious processes and can be challenging to correctly diagnose. We sought to develop a circulating biomarker panel to identify patients with severe AS. Methods:We enrolled study participants undergoing coronary or peripheral angiography for a variety of cardiovascular diseases at a single academic medical centre. A panel of 109 proteins were measured in blood obtained at the time of the procedure. Statistical learning methods were used to identify biomarkers and clinical parameters that associate with severe AS. A diagnostic model incorporating clinical and biomarker results was developed and evaluated using Monte Carlo cross-validation. Results:Of 1244 subjects (age 66.4±11.5 ?years, 28.7% female), 80 (6.4%) had severe AS (defined as aortic valve area (AVA) <1.0 ?cm2). A final model included age, N-terminal pro-B-type natriuretic peptide, von Willebrand factor and fetuin-A. The model had good discrimination for severe AS (OR=5.9, 95%?CI 3.5 to 10.1, p<0.001) with an area under the curve of 0.76 insample and 0.74 with cross-validation. A diagnostic score was generated. Higher prevalence of severe AS was noted in those with higher scores, such that 1.6% of those with a score of 1 had severe AS compared with 15.3% with a score of 5 (p<0.001), and score values were inversely correlated with AVA (r=-0.35; p<0.001). At optimal model cut-off, we found 76% sensitivity, 65% specificity, 13% positive predictive value and 98% negative predictive value. Conclusions:We describe a novel, multiple biomarker approach for diagnostic evaluation of severe AS. Trial registration number:NCT00842868.

SUBMITTER: Elmariah S

PROVIDER: S-EPMC6242008 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Elmariah Sammy S McCarthy Cian C Ibrahim Nasrien N Furman Deborah D Mukai Renata R Magaret Craig C Rhyne Rhonda R Barnes Grady G van Kimmenade Roland R J RRJ Januzzi James L JL

Open heart 20181101 2

<h4>Objective</h4>Severe aortic valve stenosis (AS) develops via insidious processes and can be challenging to correctly diagnose. We sought to develop a circulating biomarker panel to identify patients with severe AS.<h4>Methods</h4>We enrolled study participants undergoing coronary or peripheral angiography for a variety of cardiovascular diseases at a single academic medical centre. A panel of 109 proteins were measured in blood obtained at the time of the procedure. Statistical learning meth ...[more]

PMID: 30487984

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Project description:BACKGROUND:Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS:In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS:Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm?Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS:In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Dataset Information

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

Publications

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

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