(CCSP094) INCREMENTAL VALUE OF BLOOD BIOMARKERS IN CARDIAC DAMAGE STAGING CLASSIFICATION AND THE EVOLUTION OF CARDIAC DAMAGE AFTER AORTIC VALVE REPLACEMENT IN ASYMPTOMATIC AORTIC VALVE STENOSIS

Background: In patients with asymptomatic aortic stenosis (AS), a staging classification characterizing the extent of cardiac damage demonstrated strong prognostic value. This study investigated the incremental value of adding multiple blood biomarkers in the original classification and evaluated the postoperative evolution of cardiac damage in patients who underwent aortic valve replacement (AVR).

METHODS AND RESULTS: Data of 351 asymptomatic patients with mild to severe AS were retrospectively analyzed from the prospective PROGRESSA study (NCT01679431). Six blood biomarkers were measured at baseline: N-terminal pro b-type natriuretic peptide (NT-proBNP), high-sensitive cardiac troponin T (hs-cTnT), growth differentiation factor 15, suppression of tumorigenicity 2, human epididymis protein 4, and interleukin-6. Patients were also classified according to cardiac damage on echocardiography using the original classification (stage 0, no cardiac damage; stage 1, left ventricle damage; stage 2, left atrial or mitral valve damage; stage 3, pulmonary or tricuspid valve damage, and stage 4, right ventricular damage or subclinical heart failure). One hundred thirty-one (37.3%) patients were in stage 0; 52 (14.8%) in stage 1; 110 (31.3%) in stage 2; 6 (1.7%) in stage 3 and 52 (14.8%) in stage 4. Using stage 0 as referent group, blood biomarker levels at baseline increased significantly in stages 2 and 3-4 (NT-proBNP: 66, 174 and 149 pg/mL; hs-cTnT: 7, 11, and 13 ng/L; all p< 0.001). This increase remained significant for NT-proBNP in multivariate analyses adjusted for confounding factors (p < 0.001). Then, patients were reclassified at baseline using the new bonified cardiac damage staging classification with blood biomarkers. During a median follow-up of 1.65 (0.57-3.03) years, 162 (46%) patients underwent AVR, and 67 (19%) patients died. The new classification showed good discrimination between stages regarding the composite endpoint of AVR and all-cause mortality (log-rank: p=0.007). Moreover, there was a trend toward incremental value to predict the composite endpoint at 5-year over the original classification (net reclassification index=0.15; p=0.17). Eighty-two patients had a follow-up at one year post-AVR to assess the progression of cardiac damage prior to and following AVR. Eleven (13.4%) patients improved their cardiac damage stage using the new classification, 26 (31.7%) remained at the same stage, while 45 (54.9%) worsened.

Conclusion: In patients with asymptomatic AS, myocardial stress biomarkers increased as cardiac damage worsened, and the inclusion of blood biomarkers to the cardiac damage staging classification modestly improved risk stratification. Furthermore, AVR improved cardiac damage stage in a minority of patients, suggesting that early elective AVR could prevent irreversible cardiac damage.