Study Design and Population

From March 2010 to November 2021, 127 patients affected by structural valve deterioration of aortic bioprostheses underwent transfemoral VIV-TAVI at Sana Heart-Center Cottbus, Germany. A total of 19 patients (15.2%) presented preoperative moderate-to-severe or severe MR, and up to 51.2% presented with at least moderate MR evidenced by echocardiography before VIV-TAVI. A comprehensive postoperative transthoracic echocardiogram after VIV-TAVI (pre-discharge) was routinely performed. Seven patients with postoperative severe MR, two patients with previous mitral valve intervention, and four patients who died before postoperative echocardiography were excluded from this study. The remaining 114 subjects were divided into two groups according to the degree of MR: those with none or mild MR after VIV-TAVI and those with moderate MR. Inclusion and exclusion criteria are presented in the flow chart (Figure 1). Pre, intra, and postoperative data were retrospectively analyzed from the hospital database and complete follow-up was performed mainly by primary care physicians with a few interviews conducted by phone, with a mean period of 4.8 years (five months - 12 years). All clinical endpoints were defined according to the current standard for definition of the events in TAVI represented by the Valve Academic Research Consortium-3 (VARC-3) criteria^[12]. MR was defined according to the European Society of Cardiology guidelines^[8].

Fig. 1 - Study flow chart. Flow diagram depicting derivation of the final study population. MR=mitral regurgitation; VIV-TAVI=valve-in-valve transcatheter aortic valve implantation.

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Fig. 1 - Study flow chart. Flow diagram depicting derivation of the final study population. MR=mitral regurgitation; VIV-TAVI=valve-in-valve transcatheter aortic valve implantation.

VIV-TAVI Procedure

All individuals were considered at high operative risk or had contraindications for conventional surgical reoperation. A multidisciplinary local heart team consisting of an interventional cardiologist, clinical cardiologist, cardiac surgeon, and cardiac anesthesiologist carefully discussed the treatment strategy. All patients included for final analysis underwent VIV-TAVI with transfemoral access and self-expandable Medtronic device (Medtronic, Minneapolis, Minnesota, United States of America). Conscious sedation with local anesthesia was possible in 93% of patients. Twenty-nine initial procedures were performed with the Medtronic CoreValve™ (Medtronic, Minneapolis, Minnesota, United States of America), and the rest with CoreValve™ Evolut™ R valves (Medtronic). Most of the procedures (75.4%) were performed with an implantation level 4 mm below the neo-anulus, and the implantation depth did not differ in between the groups before and after propensity score matching (PSM). Thirty-eight patients with CoreValve™ Evolut™ R underwent repositioning of the prosthesis to optimize the position and in sixteen patients, the repositioning was performed ≥ 2 times. Predilatation was performed in all procedures, and postdilatation was required in seven patients (6.1%). Eligibility for VIV-TAVI, access route, type, and diameter of prosthesis were selected according to the routinely performed electrocardiographic gated multislice computed tomography with dedicated imaging software: either OsiriX (Pixmeo, Geneva, Switzerland) or 3mensio Valves (Pie Medical Imaging BV, Maastricht, the Netherlands).

Statistical Analysis

Continuous variables were expressed as the means ± standard deviation (SD) (normally distributed data) or medians with interquartile range (non-normally distributed data), while categorical variables were expressed as numbers and percentages. For continuous data, Student’s t-test or Mann-Whitney U test were used for between-groups comparisons, while categorical variables were compared with Pearson’s χ² test. To reduce the risk of selection due to the observational character of the study, a PSM was used between the groups of patients with residual moderate mitral valve regurgitation and without significant MR after VIV-TAVI. Propensity scores (PS) were generated from a logistic regression model based on the European System for Cardiac Operative Risk Evaluation II, atrial fibrillation, preoperative moderate and higher MR, preoperative higher or moderate tricuspid valve regurgitation, left atrial size, and left ventricular end-diastolic diameter and left ventricular end-systolic diameter measurements. Patients were then matched in 1:1 fashion using caliper matching method without replacement with a caliper width of 0.2 SD of the logit of the PS^[13,14]. The balance of the covariates was tested using standardized mean difference (SMD). Statistical guidelines suggest a meaningful covariate balance of the variables used to generate the PS between the two groups to be between -0.1 < SMD < 0.1^[13]. A survival analysis was performed according to the Kaplan-Meier method with the log-rank test used for comparison between groups. Statistical significance was assumed at P<0.05. Statistical analyses were conducted with the STATISTICA™ version 13 for Windows software (TIBCO StatSoft, Inc., Tulsa, Oklahoma, United States of America).

Ethics Approval

This study was approved by the Ethics Committees of the State Chambers of Physicians in Cottbus, Germany (S34(bB)/2020).

Patients’ Characteristics

Postprocedural MR improved in 51 (42.1%) patients. There was no improvement in 70 (57.9%) patients of which six (5%) presented worse MR at discharge as compared to pre-procedure echocardiography. A total of 114 patients were included in the final analysis (44.7% female, mean age 79.7±5.6 years). Patients with moderate MR after VIV-TAVI presented a higher operative risk, underwent more often several cardiac surgeries, and they were also burdened with more comorbidities such as peripheral arterial disease. Preoperative echocardiography reveled worse left ventricular ejection fraction (LVEF), more often tricuspid valve regurgitation, increased left ventricular structural dimension, and greater left atrium in moderate MR-group. PSM yielded 23 matched pairs for final comparison (all demographics and preoperative clinical data of the matched subgroups were similar). Main clinical and preoperative echocardiographic characteristics of the global population according to the baseline degree of MR are summarized in Table 1.

Table 1 - Patient demographic characteristics and preoperative echocardiographic findings.

In-Hospital Period

Technical indices such as operative time, fluoroscopy time, contrast load, failed bioprosthesis, or TAVI valve size did differ between groups and did not impact on postoperative mitral valve insufficiency. Neither Chimney technique nor bioprosthetic aortic scallop intentional laceration (BASILICA) technique nor bioprosthetic valve fracture were performed in the analyzed population. No significant differences were found between groups before and after matching in terms of intensive care unit stay, hospital stay, transient ischemic attack, stroke, postprocedural new dialysis, new-onset atrial fibrillation, myocardial infarction, and permanent pacemaker implantation. All technical aspects and the incidences of serious adverse events according VARC-3 criteria are summarized in Table 2.

Table 2 - Procedure-related variables, early outcomes according to VARC-3 definitions and echocardiographic findings at discharge.

Overall Hemodynamic Results

At discharge, the mean postoperative transvalvular pressure gradient was 15.1±8.4 mmHg and was comparable between both groups. Paravalvular leak (PVL) occurred in 44 (38.6%) patients, however, nearly 90% of them presented mild PVL, and we did not observe any severe PVL after VIV-TAVI. Both LVEF and tricuspid annular plane systolic excursion did not significantly change after VIV-TAVI, and there were no differences between groups before and after PSM (Table 2).

Long-Term Mortality

In the follow-up period, 71 (62.3%) patients survived, 59 (70.2%) of them in the none/mild MR group, and 12 (40.0%) in the moderate MR group. The overall survival probabilities at one, three, and five years were 93.7%, 71.0%, and 53.8% (Figure 2A). In the unmatched cohort, survival probabilities at one, three, and five years were 96.3% vs. 86.3%, 74.6% vs. 60.9%, and 66.0% vs. 25.0 % in the none to mild MR group vs. moderate MR group, respectively (log-rank P=0.003) (Figure 2B). In the matched cohort, survival probabilities at one, three, and five years were 95.7% vs. 87.0%, 85.0% vs. 64.5%, and 85.0% vs. 29.0% in the none to mild MR group vs. moderate MR group, respectively (log-rank P=0.035) (Figure 2C). None of the patients required repeated TAVI or MitraClip™ device implantation following VIV-TAVI during the follow-up period.

Fig. 2 - A) Kaplan-Meier survival curve of all patients. B) None/mild vs. moderate mitral regurgitation following valve-in-valve transcatheter aortic valve implantation (VIV-TAVI) before propensity score matching (PSM). C) None/mild vs. moderate mitral regurgitation following VIV-TAVI after PSM.

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Fig. 2 - A) Kaplan-Meier survival curve of all patients. B) None/mild vs. moderate mitral regurgitation following valve-in-valve transcatheter aortic valve implantation (VIV-TAVI) before propensity score matching (PSM). C) None/mild vs. moderate mitral regurgitation following VIV-TAVI after PSM.

NYHA Functional Class at Follow-up Period

NYHA class I or II was observed in 60 out of 71 (84.5%) survivors. Among survivors, we noted increased incidence of heart failure categorized as NYHA class III in the moderate MR group (n=5/12 [41.7%] vs. 6/59 [10.2%], P=0.006).

Limitations

The main limitation of this study relates to the fact that it is a retrospective non-randomized single-center study with a relatively limited sample size. The mechanism of MR is not considered in this study, although the current investigation analyzed heterogeneous group of patients with 19 different valve types used for the primary aortic valve replacement and various combinations of types and sizes of TAVI valves. During the study period, which lasted over 10 years, we observed many technical and procedural improvements in TAVI procedures, that may affect the results of the study. A further point is the learning curve, which may influence the worse outcome in the earlier years of the study period. Moreover, there were no monitoring board or core laboratory available for echocardiographic analysis, that were consequences of a retrospective nature of our study. Future multicenter randomized studies with larger samples and echocardiographic follow-up periods are warranted.