For this study, we recruited patients diagnosed with PNAR and implanted with VenusA-Valve (Venus Medtech, Hangzhou, China) or VitaFlow valve (Microport, Shanghai, China) at Zhongshan Hospital, Fudan University, from June 2018 to June 2023. All patients were considered unsuitable for surgical valve replacement after a comprehensive evaluation. In addition, all patients had a follow-up duration of $\ge$6-month and underwent cardiac ultrasound examinations. Exclusion criteria were as follows: (1) patients who had failed bioprosthetic valve surgery; (2) peak aortic valve pressure gradient measured by pre-TAVR echocardiography greater than 20 mmHg; (3) concomitant hypertrophic obstructive cardiomyopathy; (4) concomitant left ventricular thrombus or infective endocarditis. This study was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (number: B2020-039), and all patients were informed and signed a consent form.

The PH classification was as follows. Based on the pulmonary artery pressure grading criteria from previous studies [11], patients were divided by the presence of PH (pulmonary artery systolic pressure, PASP $\ge$35 mmHg) or the absence of PH (PASP 35 mmHg) according to the PASP measured by echocardiography. Clinical information of patients was collected from medical records and the catheterization laboratory information system for retrospective analysis. We documented the baseline patient information taken prior to surgery, such as hypertension, diabetes, pulmonary arterial hypertension, atrial fibrillation, heart failure, and renal insufficiency. Patients underwent multi-detector computed tomography (CT) and echocardiography examinations, and postoperative follow-up echocardiography. The parameters such as left ventricular ejection fraction, left atrial and left ventricular dimensions, degree of aortic valve regurgitation, and mean transvalvular pressure of the aortic valve were recorded. Grading of regurgitation severity was based on the valve regurgitant jet area obtained from echocardiography: Grade 0: No regurgitation or trivial regurgitation; Grade 1: Mild regurgitation; Grade 2: Moderate regurgitation; Grade 3: Severe regurgitation.

All patients underwent TAVR via intravenous anesthesia by the structural heart disease surgery team in the Department of Cardiology, Zhongshan Hospital. Patients had a post operative follow-up visit at the outpatient department after 30 days and 6 months, with transthoracic echocardiography (TTE) and electrocardiography (ECG) examinations performed, and perioperative endpoint events recorded. The definition of clinical outcomes followed the Valve Academic Research Consortium-3 (VARC-3) criteria [12]. The primary endpoints included all-cause death and cardiovascular death. The secondary endpoints included TAVR-related complications, such as myocardial infarction, major bleeding events, major vascular complications, acute kidney injury, stroke, endocarditis, new-onset atrial fibrillation, implantation of a new pacemaker, coronary artery obstruction, mild paravalvular leak, and rehospitalization.

Statistical analysis of the data was conducted using STATA (version 15.1; Stata Corporation, College Station, TX, USA). Continuous variables were expressed as mean $\pm$ standard deviation (SD) and were analyzed using either the Student’s t-test or the Mann-Whitney U test. Continuous variables in the PH and non-PH groups were compared using the Student’s t-test or the Mann-Whitney U test while categorical variables were compared using the chi-square or Fisher’s exact test. To compare baseline and post-procedure follow-up periods, continuous variables were analyzed using the paired Student’s t-test, whereas categorical variables were compared using the Wilcoxon signed-rank test. All statistical tests were two-sided, and significance was defined as p values 0.05.

In this study, 103 patients were enrolled, including 62 males and 41 females with a mean age of (72.1 $\pm$ 8.1) years. Notably, 48 (46.6%) of these patients suffered from PH. Clinical data revealed significant differences between patients with PNAR with and without PH. Patients with PH were more likely to be classified in New York Heart Association (NYHA) functional classes III and IV (93.8% vs. 76.4%, p = 0.015) and were more frequently diagnosed with renal dysfunction (10.4% vs. 0%, p = 0.014) with higher level of serum creatinine (122.2 $\pm$ 113.2 vs. 82.4 $\pm$ 22.4, p = 0.012). Additionally, they exhibited a higher Society of Thoracic Surgeons (STS) score (6.4 $\pm$ 1.9 vs. 4.7 $\pm$ 1.6, p 0.001) and elevated serum levels of Nterminal fragment of pro–brain natriuretic peptide (NT-proBNP) (2542.1 $\pm$ 2290.2 vs. 1050.4 $\pm$ 1611.7, p 0.001). However, no significant differences were observed in baseline body mass index (BMI), hypertension, diabetes, atrial fibrillation, chronic lung disease, chronic kidney disease, previous percutaneous coronary intervention, previous pacemaker implantation, or creatinine between the two groups (Table 1).

TTE examination further differentiated the two groups. Patients with PH group exhibited significantly higher PASP (44.3 $\pm$ 7.6 vs. 30.7 $\pm$ 2.6, p 0.001), lower left ventricular ejection fraction (LVEF) (51.9 $\pm$ 12.1 vs. 56.7 $\pm$ 10.4, p = 0.030), larger left ventricular end-diastolic dimension (LVEDd) (61.3 $\pm$ 10.2 vs. 55.2 $\pm$ 4.7, p 0.001), left ventricular end-systolic dimension (LVEDs) (45.7 $\pm$ 10.5 vs. 38.4 $\pm$ 6.3, p 0.001), along with a thicker end-diastolic left ventricular posterior wall (10.8 $\pm$ 1.5 vs. 10.0 $\pm$ 1.3, p = 0.005), while no notable difference was found in inter-ventricular septum thickness. Furthermore, a higher proportion of patients in the PH group exhibited moderate to severe tricuspid regurgitation (TR) (37.5% vs. 20.0%, p = 0.049). However, no significant differences were noted between these two groups in terms of mitral regurgitation (MR), mean transvalvular pressure gradient, effective regurgitant orifice area, annulus area, annulus perimeter, or the largest diameter of the ascending aorta (Table 2).

As depicted in Figs. 1,2, there was a significant improvement in cardiac function observed in both groups—those with and without PH—at 30 days and 6 months post-TAVR, compared to baseline measurements. This improvement was accompanied by a notable reduction in PASP. As shown in Table 3, compared to baseline, patients with PH demonstrated a significant decrease in PASP (35.3 $\pm$ 6.3 vs. 44.3 $\pm$ 7.6, p 0.001), average grade of MR (0.9 $\pm$ 1.1 vs. 1.7 $\pm$ 0.9, p 0.001), and average grade of TR (1.0 $\pm$ 1.1 vs. 2.0 $\pm$ 1.0, p 0.001) at 30 days post-intervention. These changes persisted significantly at 6 months, with marked decreases in PASP (34.7 $\pm$ 5.8 vs. 44.3 $\pm$ 7.6, p 0.001), average grade of MR (0.8 $\pm$ 1.0 vs. 1.7 $\pm$ 0.9, p 0.001), and average grade of TR (0.9 $\pm$ 1.0 vs. 2.0 $\pm$ 1.0, p 0.001). Furthermore, there was a significantly lower proportion of patients with moderate to severe TR at 6 months compared to baseline, though this difference was not observed at 30 days. For the group without PH, similar significant reductions in PASP, MR, and TR were recorded at both the 30-day and 6-month follow-ups compared to baseline. Additionally, both groups experienced a notable reduction in the proportion of patients with moderate to severe AR during the 30-day and 6-month of follow-ups, while there were no significant changes in LVEF.

Fig. 1.

Changes in the NYHA functional classification in PNAR patients Pre- and Post-TAVR, with and without PH. Assessment of the NYHA functional class changes in patients with PNAR undergoing TAVR, categorized by the presence or absence of PH. (A) illustrates the progression in patients without PH, while (B) details those with PH. These comparisons highlight the procedural impact on cardiac functional status over the follow-up period. Abbreviations: PH, pulmonary artery hypertension; TAVR, transcatheter aortic valve replacement; NYHA, New York Heart Association; PNAR, pure native aortic regurgitation.

Fig. 2.

Changes in PASP pre- and post-TAVR in PNAR patients, segregated by PH status. Comparison of PASP before and after TAVR in patients with PNAR, differentiated by the absence (A) or presence (B) of PH. The figure underscores the procedural impact on PASP across both patient categories over the follow-up period, demonstrating the effectiveness of TAVR in modifying hemodynamic parameters. Abbreviations: PH, pulmonary artery hypertension; TAVR, transcatheter aortic valve replacement; PASP, systolic pulmonary artery pressure; PNAR, pure native aortic regurgitation.

There was no significant difference in primary and secondary endpoints in PNAR patients with or without PH who underwent TAVR. Notably, there were no instances of all-cause or cardiac death in either group. The incidence of major in-hospital adverse events was as follows: major bleeding, major vascular complications, stroke, and new-onset atrial fibrillation, new-onset left bundle branch block, new-onset atrioventricular block, permanent pacemaker implants, and mild paravalvular leaks were 2.1%, 0%, 2.1%, 2.1%, 12.5%, 27.1%, 29.2%, and 14.6% in the group with PH and 0%, 0%, 0%, 7.3%, 21.8%, 20.0%, 16.4%, and 5.5% in the group without PH.

During the 6 months follow-up period, hospital admissions were slightly higher in the PH group (3 patients) compared to the control group (1 patient). Additionally, the group with PH exhibited a prevalence of 2.1% for major bleeding events, 4.2% for strokes, 6.3% for permanent pacemaker implants and new-onset atrioventricular block, and 12.5% for mild paravalvular leaks. The group without PH demonstrated a prevalence of 1.8% for new-onset left bundle branch block, 10.9% for new-onset atrioventricular block, 3.6% for new permanent pacemaker implants and 9.1% for mild para-valvular leaks. This data is summarized in Table 4.

Our study is subject to certain limitations that merit consideration. Firstly, it is a retrospective analysis conducted at a single-center, it features a relatively small cohort, and the follow-up period was limited to 6 months. Such constraints may affect the generalizability of the results and underscore the need for larger, multi-center, prospective studies with extended follow-up durations to validate our findings. Secondly, the assessment of PASP was performed using echocardiography, as opposed to right heart catheterization, which is regarded as the gold standard for this measurement. Consequently, the estimated PASP values may lack the precision achievable through catheterization, potentially affecting the accuracy of our PH evaluations. Additionally, patients with extremely severe PH were excluded from this study due to their ineligibility for TAVR based on our selection criteria. This exclusion limits our insights into the outcomes of TAVR in this particularly high-risk patient subgroup, indicating a gap in current research that future studies could aim to address.