TIMING AND DETERMINANTS OF THE DETERIORATION OF FUNCTIONAL STATUS IN PATIENTS WITH AORTIC STENOSIS

BACKGROUND The assessment of changes in symptomatic/functional status during follow-up is critical to determine the optimal timing for intervention in asymptomatic patients with severe aortic valve stenosis (AS). However, there is very few data on the correlation between the progression of AS severity and the deterioration of symptomatic status. Fast progression of hemodynamic severity of AS (i.e. annualized progression of peak jet velocity [Vpeak] ≥30 cm/s) is among the risk markers (Class IIa) recommended in the guidelines to trigger early intervention in asymptomatic severe AS. We investigated the association between the progression of AS hemodynamic severity and the change in functional status during follow-up of patients with asymptomatic mild-to-moderate AS at baseline. METHODS AND RESULTS 285 patients with AS (mean age 65±13 years, 28% women) prospectively recruited in the PROGRESSA study (NCT01679431) were included in this analysis. Functional status was evaluated using the New York Heart Association (NYHA) classification. Baseline NYHA class was similar (class I, II, III: 57%, 41%, 2% versus 58%, 41%, 1%; p=0.75) between patients with moderate (i.e. Vpeak progression ≥12 cm/s/year; median of cohort) versus those with slow AS progression rate. During a mean follow-up time of 3.9±2.4 years, patients with moderate AS progression rate had larger increase in NYHA class compared to those with slow progression (+0.13±0.48 versus +0.01±0.21 class/year; p=0.008). From baseline to 2 years, a significant worsening of NYHA class occurred but only in the moderate AS progression group (Figure 1). In comprehensive multivariable analysis, AS progression rate remained significantly associated with the annualized change in NYHA class (p=0.04). A total of 156 clinical events (110 AVR and 46 deaths) occurred during a mean follow-up of 1.1±1.5 years after the last echocardiographic visit. Patients with an increase of at least one NYHA class (n=70) had significantly higher risk of events (adjusted hazard ratio: 1.75 [95% confidence interval: 1.12-2.75]; p=0.01). CONCLUSION In this prospective cohort of patients with mild-to-moderate AS at baseline, a moderate progression rate of AS severity was associated with a significant deterioration of patients’ functional status at 2 years follow-up and with increased risk of major adverse clinical events, thereafter. The decline in functional status often occurs early in the course of the disease and is in large part determined by the progression rate of AS hemodynamic severity.