Arterial Wave Reflection and Aortic Valve Stenosis: Diagnostic Challenges and Prognostic Significance

Abstract

Introduction: Arterial wave reflection is an important component of the left ventricular afterload, affecting both pressure and flow to the aorta. The aim of the present study was to evaluate the impact of wave reflection on transvalvular pressure gradients (TPG), a key parameter for the evaluation of aortic valve stenosis (AS), as well as its prognostic significance in patients with AS undergoing a transcatheter aortic valve replacement (TAVR).

Materials and methods: The study population consisted of 351 patients with AS (mean age 84 ± 6 years, 43% males) who underwent a complete hemodynamic evaluation before the TAVR. The baseline assessment included right and left heart catheterization, transthoracic echocardiography, and a thorough evaluation of the left ventricular afterload by means of wave separation analysis. The cohort was divided into quartiles according to the transit time of the backward pressure wave (BWTT). Primary endpoint was all-cause mortality at 1 year.

Results: Early arrival of the backward pressure wave was related to lower cardiac output (Q1: 3.7 ± 0.9 lt/min vs Q4: 4.4 ± 1.0 lt/min, p < 0.001) and higher aortic systolic blood pressure (Q1: 132 ± 26 mmHg vs Q4: 117 ± 26 mmHg, p < 0.001). TPG was significantly related to the BWTT, patients in the arrival group exhibiting the lowest TPG (mean TPG, Q1: 37.6 ± 12.7 mmHg vs Q4: 44.8 ± 14.7 mmHg, p = 0.005) for the same aortic valve area (AVA) (Q1: 0.58 ± 0.35 cm² vs 0.61 ± 0.22 cm², p = 0.303). In multivariate analysis, BWTT remained an independent determinant of mean TPG (beta 0.3, p = 0.002). Moreover, the prevalence of low-flow, low-gradient AS with preserved ejection fraction was higher in patients with early arterial reflection arrival (Q1: 33.3% vs Q4: 14.9%, p = 0.033). Finally, patients with early arrival of the reflected wave (Q1) exhibited higher all-cause mortality at 1 year after the TAVR (unadjusted HR: 2.33, 95% CI: 1.17-4.65, p = 0.016).

Conclusion: Early reflected wave arrival to the aortic root is associated with poor prognosis and significant aortic hemodynamic alterations in patients undergoing a TAVR for AS. This is related to a significant decrease in TPG for a given AVA, leading to a possible underestimation of the AS severity.

Keywords: aortic valve stenosis; arterial hypertension; arterial stiffness; arterial wave reflection; transvalvular pressure gradients.

FIGURE 1

Schematic representation describing the principle of the arterial wave reflection theory and the effects on pressure and flow contour waveform by the reflected waves. P, pressure; Q, blood flow.

FIGURE 2

Study flowchart. TAVR, transcatheter aortic valve replacement; LVOT, left ventricular outflow tract.

FIGURE 3

Pressure and flow wave separation analysis for two study participants from the Q1 (A) and the Q4 (B) groups. Pressure and flow wave separation analysis in a patient with an early (transit time 0.041 s, reflection magnitude 66%, panels A1,A2) and a late reflection wave arrival (transit time 0.167 s, reflection magnitude 49%, B1,B2) with the same AVA (0.55 cm²). Early reflection arrival is associated with a much more prominent deceleration of the aortic flow due to the backward wave and a decreased SV (A2 vs. B2, 47 ml vs 68 ml accordingly). In addition, early arrival is associated with increased aortic pressure during systole, with left ventricular pressure being comparable between the two patients (A1 vs. B1).

FIGURE 4

Aortic stenosis classification and incidence of the low-flow, low-gradient severe AS with preserved EF according to the BWTT quartiles. AS, aortic stenosis; AVA, aortic valve area; AVAi, aortic valve area indexed for body surface area; EF, ejection fraction; TPG, transvalvular pressure gradient; SVi, stroke volume indexed for body surface area.

FIGURE 5

Multiple linear regression analysis examining the independent effect of the BWTT on transvalvular pressure gradients obtained by either echocardiographic or invasive evaluation. Independent variables: Aortic systolic blood pressure; Aortic valve area (estimated by the Gorlin formula); Aortic characteristic impedance; Systemic vascular resistance; Total arterial compliance; gender and height.

FIGURE 6

Kaplan-Meier curves for all-cause mortality at 1 year according to BWTT quartiles. Model A: adjusted HR = 2.38 (95% CI: 1.16–4.89, p = 0.018), covariates: gender and STS Score. Model B: adjusted HR = 2.00 (95% CI: 0.95–4.24, p = 0.064), covariates: gender, STS Score and tricuspid regurgitation. Model C: adjusted HR = 2.24 (95% CI: 1.12–4.47, p = 0.022), covariates: Device success. TAVR: transcatheter aortic valve replacement.