Impact of concomitant mitral regurgitation on transvalvular gradient and flow in severe aortic stenosis: a systematic ex vivo analysis of a subentity of low-flow low-gradient aortic stenosis

Abstract
Aims: Evaluation of aortic stenosis (AS) is based on echocardiographic measurement of mean pressure gradient (MPG), flow velocity (V-max) and aortic valve area (AVA). The objective of the present study was to analyse the impact of systemic haemodynamic variables and concomitant mitral regurgitation (MR) on aortic MPG, V-max and AVA in severe AS. Methods and results: A pulsatile circulatory model was designed to study function and interdependence of stenotic aortic (AVA: 1.0 cm(2), 0.8 cm(2) and 0.6 cm(2)) and insufficient mitral prosthetic valves (n=8; effective regurgitant orifice area [EROA] 0.4 cm(2)) using Doppler ultrasound. In the absence of severe MR, a stepwise increase of stroke volume (SV) and a decrease of AVA was associated with a proportional increase of aortic MPG. When MR with EROA 0.4 cm(2) was introduced, forward SV decreased significantly (70.9 +/- 1.1 ml vs. 60.8 +/- 1.6 ml vs. 47.4 +/- 1.1 ml; p=0.02) while MR volume increased proportionally. This was associated with a subsequent reduction of aortic MPG (57.1 +/- 9.4 mmHg vs. 48.6 +/- 13.8 mmHg vs. 33.64 +/- 9.5 mmHg; p=0.035) and V-max (5.09 +/- 0.4 m/s vs. 4.91 +/- 0.73 m/s vs. 3.75 +/- 0.57 m/s; p=0.007). Calculated AVA remained unchanged (without MR: AVA=0.53 +/- 0.04 cm(2) vs. with MR: AVA=0.52 +/- 0.05 cm(2); p=ns). In the setting of severe AS without MR, changes of vascular resistance (SVR) and compliance (C) did not impact on aortic MPG (low SVR and C: 66 +/- 13.8 mmHg and 61.1 +/- 20 mmHg vs. high SVR and C: 60.9 +/- 9.2 mmHg and 71.5 +/- 13.5 mmHg; p=ns) In concomitant severe MR, aortic MPG and V-max were not significantly reduced by increased SVR (36.6 +/- 2.2 mmHg vs. 34.9 +/- 5.6 mmHg, p=0.608; 3.89 +/- 0.18 m/s vs. 3.96 +/- 0.28 m/s; p=ns). Conclusions: Systemic haemodynamic variables and concomitant MR may potentially affect diagnostic accuracy of echocardiographic AS evaluation. As demonstrated in the present study, MPG and V-max are flow-dependent and significantly reduced by a reduction of forward SV from concomitant severe MR, resulting in another entity of low-flow low-gradient aortic stenosis. In contrast, calculated AVA appears to be a robust parameter of AS evaluation if severe MR is present. Changes of SVR and C did not affect the diagnostic accuracy of AS evaluation.

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