Prognostic value of low-dose dobutamine testing in asymptomatic patients with moderate or severe aortic stenosis and preserved ejection fraction

Abstract

Purpose: In Aortic Stenosis (AS) most Doppler-echocardiographic indices that are used for assessing AS severity are flow dependent. The aim of this study was to assess prognostic value of low-dose Dobutamine Testing (DT) in patients with moderate or severe AS and preserved Ejection Fraction (EF). Method: A total of 126 asymptomatic patients with aortic valve area (AVA) ≤1.5 cm2 and EF >50% were enrolled in this prospective study. The follow-up period was 14±2 months. Mean age was 66.47±10.53; (58.73% males), mean EF was 72,03±6,69%, mean pressure gradient (Pmean) 41.94±11.22 mmHg and mean AVA 0.82±0.22 cm2. Patients with ≥2+ valvular regurgitation or more than mild mitral stenosis were excluded. The dobutamine infusion protocol was begun at 5 μg/kg/min body weight up to 20 μg/kg/min, titrated upwards at steps of 5 μg/kg/min every 3 min. The composite outcome endpoint (MACE) was defined as cardiac death, aortic valve replacement and hospitalization caused by AS symptoms according to patient's medical record. Results: No patient experienced a serious adverse event during or after DT. A total of 70 patients had MACE (55.55%), of which 9 patients (7.14%) have died during follow-up. Out of 70 patients, 56 patients (80%) had an Aortic Valve Replacement (RAV). Patients who had an increase in AVA during DT ≤0.2 cm2 and/or final AVA ≤1 cm2 had more often RAV (hi=9.5311; df=1; p=0.002). The lasso penalized Cox regression, conducted solely on the variables at rest, showed that the greatest predictive capacity has the aortic valve resistance (AVR). At the same time, the AUC for the all analyzed pre-dobutamine variables combined, evaluated at time = 12 months, was 0.76. On the other hand, the L1 procedure, when applied on all variables (pre and during DT), chooses only dobutamine variables as the most valuable in predictive sense, improving AUC by 6% (AUC =0.82, at time = 12 months). The value of the AVR obtained during the DT was the strongest independent one-year MACE predictor (according to bootstrapped p values) of all pre and during DT varaibles, with the value of 195.12 dynes s cm-5 having the highest sensitivity ans specificity in predicting MACE (0.78 and 0.73 respectively). In addition, patients who have experienced symptoms (11/126, 8.73%) during DT had more often MACE comparing to asymptomatic patients (hi=6,7408; p<0,001; df=1). Conclusion: The present study demonstrates that AVR, as well as flow-mediated changes during DT, can provide new, clinically relevant information in terms of outcome and timing of valve replacement in asymptomatic patients with moderate and severe AS and preserved EF.