Pressure gradient vs. flow relationships to characterize the physiology of a severely stenotic aortic valve before and after transcatheter valve implantation

Abstract

Aims: Echocardiography and tomographic imaging have documented dynamic changes in aortic stenosis (AS) geometry and severity during both the cardiac cycle and stress-induced increases in cardiac output. However, corresponding pressure gradient vs. flow relationships have not been described.

Methods and results: We recruited 16 routine transcatheter aortic valve implantations (TAVI's) for graded dobutamine infusions both before and after implantation; 0.014″ pressure wires in the aorta and left ventricle (LV) continuously measured the transvalvular pressure gradient (ΔP) while a pulmonary artery catheter regularly assessed cardiac output by thermodilution. Before TAVI, ΔP did not display a consistent relationship with transvalvular flow (Q). Neither linear resistor (median R2 0.16) nor quadratic orifice (median R2 < 0.01) models at rest predicted stress observations; the severely stenotic valve behaved like a combination. The unitless ratio of aortic to left ventricular pressures during systolic ejection under stress conditions correlated best with post-TAVI flow improvement. After TAVI, a highly linear relationship (median R2 0.96) indicated a valid valve resistance.

Conclusion: Pressure loss vs. flow curves offer a fundamental fluid dynamic synthesis for describing aortic valve pathophysiology. Severe AS does not consistently behave like an orifice (as suggested by Gorlin) or a resistor, whereas TAVI devices behave like a pure resistor. During peak dobutamine, the ratio of aortic to left ventricular pressures during systolic ejection provides a 'fractional flow reserve' of the aortic valve that closely approximates the complex, changing fluid dynamics. Because resting assessment cannot reliably predict stress haemodynamics, 'valvular fractional flow' warrants study to explain exertional symptoms in patients with only moderate AS at rest.

Figure 1

Protocol set-up. After routine transcatheter aortic valve implantation preparation, we placed 0.014″ commercial pressure wires in the ascending aorta and across the aortic valve (dashed white line) in the left ventricle to provide high fidelity and uninterrupted measurements of the transvalvular pressure gradient (ΔP). A standard 7F pulmonary artery (Swan-Ganz) catheter enabled thermodilution assessment of cardiac output, while a transoesophageal echocardiographic probe permitted non-invasive evaluation. The upper panels depict the pictorial and fluoroscopic set-up, while the lower panels display the acquired pressure signals and graded dobutamine infusion. Automated analysis identified the start of each beat as well as the ejection period (large black dots in the lower left panel) to compute mean pressures and gradients (highlighted portions of the first beat) as well as the relative duration of ejection (marked for the second beat).

Figure 2

Example haemodynamic data and analysis. The left panel depicts several haemodynamic parameters during the time-course of the protocol. Each small dot represents the systolic ejection portion of a single cardiac cycle, as in Figure1, with a superimposed trend line. Thermodilution cardiac output measurements (orange dots) were made twice during each stage of dobutamine infusion. The right panel demonstrates how each measurement of cardiac output and mean transvalvular gradient (ΔP) was transformed into a single point, creating a pressure loss vs. flow curve. In this example, the shape of the curve before transcatheter aortic valve implantation is neither quadratic (as assumed by the Gorlin orifice model) nor linear (as for a resistor), but instead a mixture of the two. However, after transcatheter aortic valve implantation (raw data not shown but provided in the Supplementary material online and similar in concept to the left panel) the points fall on a straight line through the origin, implying a constant valve resistance.

Take home figure

Conceptual framework for aortic stenosis physiology. The shape of curve linking systolic ejection transvalvular pressure gradient (ΔP) to transvalvular flow (Q) provides a physiologic ‘fingerprint’ of haemodynamics unique to that stenotic valve. A single rest measurement (coloured blue) cannot predict which path will be observed during dobutamine stress (coloured red). Five patterns of increasing severity can be anticipated, from most severe (worse than the quadratic shape assumed by the Gorlin orifice model) to least severe (better than the linear shape of a resistor). Three examples from the cohort, plus the example in the right panel of Figure 2, provide visual evidence of the heterogeneity of valvular pathophysiology.

Figure 3

Relationships with flow reduction from aortic stenosis. For the 13 subjects with successful paired assessments before and after transcatheter aortic valve implantation, we can estimate the flow reduction due to the stenotic aortic valve since systemic vascular resistance during systolic ejection remains constant during peak dobutamine (see Supplementary material online). The stress aortic valve index, equal to the aortic/left ventricular pressure ratio during systolic ejection, shows the best correlation (solid red lines denote 95% confidence ellipses), with stress assessments performing better than resting assessments and unitless ratios performing better than their corresponding absolute gradients with intermediate performance for the aortic valve area.

Figure 4

Baseline vs. stress valve haemodynamics. Before transcatheter aortic valve implantation (red points) all subjects except one had an aortic/left ventricular ratio during systole of 0.7 or less. After transcatheter aortic valve implantation (blue points) all implants except one had a stress aortic/left ventricular systolic pressure ratio (stress aortic valve index) greater than 0.7. Heterogeneity existed between baseline and stress aortic valve index measurements; some native valves or implants showed little change (grey area within 0.03 of equality) while others showed large changes. Receiver operating characteristic curve analysis found an optimal threshold at 0.71 to separate pre- and post-transcatheter aortic valve implantation assessments with a large area under the curve of 0.97 (95% confidence interval 0.92–1.0).