Asymptomatic severe aortic stenosis and preserved left ventricular ejection fraction: role of the interaction between longitudinal function and valvulo-arterial impedance in the risk stratification

Purpose: We investigated whether the global left ventricular (LV) afterload may influence myocardial strain more extensively than the severity of valve disease in a prospective cohort of asymptomatic patients (pts) with severe aortic stenosis (AS) and preserved LV ejection fraction (EF), and whether the global afterload and longitudinal strain (LS) may be considered new prognostic markers of clinical outcome in these pts. Methods: 52 pts (73±10 yrs) were studied. By speckle tracking echocardiography and the AFI (automated function imaging) tool, regional and global LS, radial (RS), circumferential strain (CS), rotations, twist and untwisting rate were assessed. As a measure of global LV afterload, we calculated the valvulo-arterial impedance (Zva). Predefined end-points for assessing the outcome were the occurrence of symptoms, aortic valve replacement (AVR) or death. Results: All pts had a severe AS (indexed aortic valve area: 0.4±0.1 cm2/m2; mean gradient: 60±16 mmHg) with a LV concentric hypertrophy (LV mass index: 127±38g /m2; relative wall thickness:0.58±2) and a normal EF (61±5%). Zva was increased: 5.8±2 mmHg/mL/m2. The mean F.U. time was 11±7.5 months. F.U. information was available in 38/52 (73%) pts. Predefined end-points were reached in 26 pts (2 deaths, 2 pts with dyspnea, 22 pts who required AVR). Twelve pts remained asymptomatic. At the Mann-Whitney test, LVEF and all parameters of AS severity were similar in the two groups whereas LS (-13±2 vs -18±3%, p<0.001) and Zva (6.7±3 vs 4.2±0.8 mmHg/mL/m2, p<0.001) were impaired in pts who developed an event in comparison with asymptomatic pts. Neither RS, CS, rotations or twist differed between groups. Interestingly, Zva was related with both global CS (r=0.59, p=0.02) and global LS (r=0.56, p=0.04), whereas any relationship was found between aortic pressure gradients and myocardial strains and/or rotations. With univariable Cox regression, predictors of events were: LVEF (p=0.02), mass index (p=0.01), LS (p<0.0001), RS (0.04) and Zva (p=0.0002). With multivariable analysis only global LS (p=0.03) and Zva (p=0.03) were independently associated with the combined end-point. Using receiver-operator characteristic curve analysis a LV global LS ≤ -18% (AUC=0.87, sensitivity=96%, specificity= 73%) and a Zva ≥4.7 mmHg/ml/m2 (AUC=0.98, sensitivity=100%, specificity= 91%) were identified as the best cut-off values to be associated with events. Conclusions: The prognosis of pts with asymptomatic AS depends not only on stenosis severity but also on the level of global afterload and its consequences on myocardial function.