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.

Introduction: Pulmonary hypertension (PH), traditionally defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg, is associated with poor outcomes in patients undergoing a transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Recently, a novel definition for PH has been proposed, placing the cut-off value of mean PAP at 20 mmHg, and introducing pulmonary vascular resistance as an exclusive indicator for the pre-capillary involvement. In light of the novel criteria, whether PH still preserves its prognostic significance remains unknown. Methods: The study population consisted of 380 patients with AS, who underwent a right heart catheterization before TAVR. The cohort was divided according to the presence of PH (n = 174, 45.7%) or not. Patients with PH were further divided into the following groups: (1) Pre-capillary PH ((Pre-capPH), n = 46, 12.1%); (2) Isolated post-capillary PH ((IpcPH), n = 78, 20.5%); (3) Combined pre and post-capillary PH ((CpcPH), n = 82, 21.6%). The primary endpoint was all-cause mortality at 1 year. Results: A total of 246 patients (64.7%) exhibited mean PAP > 20 mmHg. Overall, the presence of PH was associated with higher 1-year mortality rates (hazard ratio (HR) 2.8, 95% CI: 1.4–5.8, p = 0.004). Compared to patients with no PH, Pre-capPH and CpcPH (but not IpcPH) were related to higher 1-year mortality (HR 2.7, 95% CI: 1.0–7.2, p = 0.041 and HR 3.9, 95% CI: 1.8–8.5, p = 0.001, respectively). This remained significant even after the adjustment for baseline comorbidities. Conclusions: Pre-interventional PH according to the novel hemodynamic criteria, is linked with poor outcomes in patients undergoing TAVR for severe AS. However, this is mainly driven by patients with mean PAP ≥ 25 mmHg. Patients with a pre-capillary PH component as defined by increased PVR present an even worse prognosis as compared to patients with isolated post-capillary or no PH who present comparable 1-year mortality rates.

The transaortic valvular pressure gradient (TPG) plays a central role in decision-making for patients suffering from severe aortic stenosis. However, the flow-dependence nature of the TPG makes the diagnosis of aortic stenosis challenging since the markers of cardiac performance and afterload present high physiological interdependence and thus, isolated effects cannot be measured directly in vivo. We used a validated 1D mathematical model of the cardiovascular system, coupled with a model of aortic stenosis, to assess and quantify the independent effect of the main left ventricular performance parameters (end-systolic (E_es) and end-diastolic (E_ed) elastance) and principal afterload indices (total vascular resistance (TVR) and total arterial compliance (TAC)) on the TPG for different levels of aortic stenosis. In patients with critical aortic stenosis (aortic valve area (AVA) ≤ 0.6 cm²), a 10% increase of E_ed from the baseline value was associated with the most important effect on the TPG (−5.6 ± 0.5 mmHg, p < 0.001), followed by a similar increase of E_es (3.4 ± 0.1 mmHg, p < 0.001), in TAC (1.3 ±0.2 mmHg, p < 0.001) and TVR (−0.7 ± 0.04 mmHg, p < 0.001). The interdependence of the TPG left ventricular performance and afterload indices become stronger with increased aortic stenosis severity. Disregarding their effects may lead to an underestimation of stenosis severity and a potential delay in therapeutic intervention. Therefore, a comprehensive evaluation of left ventricular function and afterload should be performed, especially in cases of diagnostic challenge, since it may offer the pathophysiological mechanism that explains the mismatch between aortic severity and the TPG.