Design and Population

We retrospectively analyzed 86 consecutive high-risk patients with degenerated aortic bioprostheses who underwent TAVI-ViV between March 2010 and July 2019 at Sana Heart Center in Cottbus, Germany. All patients were discussed by the Heart Team consisting of a cardiac surgeon, an interventional cardiologist, and cardiac anesthesiologists and they were disqualified from a conventional repeat surgery due to a high-risk profile. Individuals with acute endocarditis, requiring concomitant cardiac procedures, with previously implanted mechanical or transcatheter valves were excluded. One patient was excluded due to the intraoperative death caused by a perforation of the left ventricle by the guidewire. Finally, 85 patients met the eligibility criteria and were included in the study. The cohort was divided into two groups — group A, with postprocedural mean pressure gradient (PG) ≥ 20 mmHg, and group B, with mean PG < 20 mmHg. The protocol for this study was approved by an institutional review board (ethics committee approval number S-17(dB)/2020) and an individual patient consent was not required due to the retrospective nature of this investigation.

Data Collection and Outcomes

Our Heart Team, which consisted of a cardiac surgeon, a cardiologist, and an anesthesiologist, always carefully analyzed the treatment strategy. The size of the valves was chosen after an analysis of the multi-slice computed tomography with dedicated OsiriX imaging software (Pixmeo, Geneva, Switzerland). All procedures were performed using the balloon-expandable Medtronic valves (Medtronic, Minneapolis, Minnesota, United States of America [USA]). All demographics, preoperative clinical data, procedural and in-hospital postprocedural data, echocardiography at discharge data, and phone interview follow-up were collected to build the database. Pre-discharge transthoracic echocardiography was performed on the postoperative days 4-13. A complete follow-up was performed mainly by family physicians with a few interviews conducted by phone, with a mean period of 3.8 years (2.1 month to 9.6 years). The primary aim of this investigation was to identify the risk factors of high residual gradient and investigate the effect of the residual transaortic gradient on the overall survival, New York Heart Association (NYHA) functional class, and freedom from aortic valve re-intervention. Secondary objectives were an evaluation of the following: 30-day mortality, early complications (< 30 postoperative days), echocardiographic outcomes (aortic regurgitation, left ventricular ejection fraction), and intensive care unit (ICU) as well as in-hospital length of stay.

Statistical Analysis

Continuous variables were expressed as means ± standard deviation, while categorical variables were expressed as number and percentages. For continuous data, the Student’s t-test or Mann-Whitney’s U-test were used for between groups comparisons, while categorical variables were compared with Pearson χ² test. To identify the independent predictors of high residual gradient (meanPG ≥ 20 mmHg) after TAVI-ViV, we built a multivariate logistic regression model for the whole cohort by using all preoperative variables presented in Table 1 in addition to intraoperative indices such as implantation height or valve type (CoreValve™ or Evolut™ R). A multivariate logistic regression analysis was performed using a stepwise backward regression including only factors identified during the univariate analysis with a P-value ≤ 1. Survival curves were calculated using the Kaplan-Meier estimator and the comparison between both groups was made using the log-rank test (Mantel-Cox test). Statistical significance was assumed at P<0.05. The statistical analysis was computed with STATISTICA ver. 13 for Windows software (TIBCO StatSoft, Inc., Tulsa, Oklahoma, USA).

Table 1 - Patients’ demographic, clinical, and echocardiographic characteristics.

Baseline Characteristics

A total of 85 patients were included in the final analysis (45.9% male, mean age 79.8 ± 5.7 years, European System for Cardiac Operative Risk Evaluation II 11.8 ± 6.0%). All demographics and preoperative clinical data of the study population were summarized in Table 1. During the postprocedural echocardiography on days 4-13 after TAVI-ViV, high residual gradient was observed in 21 patients (24.7%). In patients with higher postoperative meanPG, a history of patient-prosthesis mismatch (PPM) after initial surgery, higher gradients pre TAVI-ViV, and smaller and stented degenerated valves were significantly more prevalent.

Operative Data

The procedure was performed mainly using the femoral approach (97.6%) and conscious sedation with local anesthesia (91.8%). Pre-dilatation was a standard manner and post-dilatation was required in three patients to get the fully expanded valve. No neurological protection, coronary protection system, or valve fracture were used. All implanted valves were self-expandable, CoreValve™ (38.8%) or CoreValve™ Evolut™ R (61.2%). Repositioning of the valve was possible only in the new generation valve (CoreValve™ Evolut™ R) and was needed approximately in half of these patients. Procedures resulting in higher postprocedural meanPG were performed more often with the older valve type, lasted significantly longer, and the new valve was implanted deeper (Table 2).

Table 2 - Technical indices.

Risk Factors of High Residual Gradient

In the univariate analysis, preoperative gradient, pre-existing PPM, deep valve implantation, small degenerated valves, and older generation of transcatheter aortic valves were found to be risk factors for high residual gradient (Figure 1). In the multivariate analysis, preexisting maxPG > 60 mmHg (odds ratio [OR]: 9.3; 95% confidence interval [CI] 1.7-50.9; P=0.010), implantation level of 4 mm below neo-annulus (OR: 0.089; 95% CI 0.016-0.494; P=0.006), and degenerated valve size ≤ 23 mm (OR: 20.3; 95% CI 1.719-240.2; P=0.017) were independent predictors of high residual gradient (Table 3).

In-hospital Outcomes

Four patients (4.7%) died during the first 30 days after the procedure, one patient in group A and three patients in group B (P=0.989). There were no differences in the ICU stay, in-hospital stay, and complication rates between the groups. Kidney function improved after the procedure, regardless of postprocedural mean gradient (Groups A +18.4% vs. +14.4% Group B, P=0.243). Twenty-six patients (30.6%) had postoperative paravalvular leak, four in group A and 19 in group B. Moderate paravalvular leak occurred in three patients in group B. There were no cases of postprocedural severe paravalvular leak. Early complications (< 30 days post TAVI-ViV) are summarized in Table 4.

Fig. 1 - Univariate analysis of factors associated with high residual gradients after transcatheter aortic valve-in-valve implantation (by forest plot representation).

Fig. 1 - AF=atrial fibrillation; BMI=body mass index; BSA=body surface area; CI=confidence interval; COPD=chronic obstructive pulmonary disease; DM=diabetes mellitus; EF=ejection fraction; LA=left atrial; LVIDd=left ventricular internal dimension in diastole; LVIDs=left ventricular internal dimension in systole; PG=pressure gradient; PPM=patient-prosthesis mismatch; PVD=peripheral vascular disease; SPAP=systolic pulmonary artery pressure.

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Fig. 1 - Univariate analysis of factors associated with high residual gradients after transcatheter aortic valve-in-valve implantation (by forest plot representation).

Fig. 1 - AF=atrial fibrillation; BMI=body mass index; BSA=body surface area; CI=confidence interval; COPD=chronic obstructive pulmonary disease; DM=diabetes mellitus; EF=ejection fraction; LA=left atrial; LVIDd=left ventricular internal dimension in diastole; LVIDs=left ventricular internal dimension in systole; PG=pressure gradient; PPM=patient-prosthesis mismatch; PVD=peripheral vascular disease; SPAP=systolic pulmonary artery pressure.

Table 3 - Univariate and multivariate analyses of risk factor for high residual gradient following self-expandable TAVI-ViV.

Follow-up Period

Twenty-seven patients (31.8%) died during the study period over nine years. Kaplan-Meier estimated that the survival rate after one, two, and five years was 87.7%, 81.5%, and 61.7%, respectively. The postoperative transaortic gradient had no impact on survival — group A vs. group B: one-year survival rate 85.7% vs. 88.4%, two-year survival rate 80.0% vs. 81.9%, and five-year survival rate 62.9% vs. 59.3%, P=0.938 (Figure 2). Approximately 40% of deaths (11/27) were caused by a cardiac reason. Two out of eight (25%) deaths in group A and nine out of 19 (47.4%) deaths in group B were cardiac related. Cumulative cardiac death-free survival in one, two, and five years were comparable in both groups — group A vs. group B: one-year survival rate 95.2% vs. 93.6%, two-year survival rate 88.9% vs. 86.7%, and five-year survival rate 88.9% vs. 83.9%, P=0.442 (Figure 3). At the end of the follow-up period, 50 out of 58 survivors (86.2%) were found in NYHA I or II functional classes (group A 69.2% vs. group B 91.1%, P=0.044). One survivor with discharge meanPG 30 mmHg was found in NYHA Class IV seven years after TAVI-ViV and required re-TAVI-ViV.

Limitations

This analysis has several limitations. It is a single-center study with a relatively small sample size. The main limitations of this study are the lack of randomization of the treated groups and the retrospective nature of this investigation. Another limitation is the absence of PPM evaluation following TAVI-ViV and echocardiographic results during the follow-up period. Larger studies will be needed to confirm these results, especially a randomized controlled trial to evaluate the results of intermediate risk patients with degenerated bioprostheses.