Introduction
Transcatheter aortic valve implantation (TAVI) has emerged as an alternative therapy for
patients with severe aortic stenosis who are inoperable or high-risk candidates for surgical aortic valve replacement.1 Since the first-in-man procedure in 2002,2 several improvements have been achieved in TAVI device technologies and procedural management, leading to incremental success rates.3-5 Early and mid-term echocardiographic follow-up after TAVI has shown an excellent hemodynamic performance of these bioprostheses, but a relevant prevalence of post-procedural paravalvular leak (PVL) has been consistently reported, with potential clinical consequences that need to be explored.4-11 Although PVL is usually trivial or mild in the majority of patients receiving either one of the available TAVI prostheses, the incidence of moderate/severe PVL is significantly higher than following surgical aortic valve replacement, ranging between 5% and 40%, and being more common with the Medtronic CoreValve
(Medtronic, Minneapolis, MN) than with the Edwards SAPIEN (Edwards Lifesciences, Irvine, California),4-11 The mechanisms commonly appointed as cause of PVL are the inadequate expansion of the prosthesis and its incomplete sealing within the aortic annulus because of the presence of prominent eccentric calcifications. The interest in PVL after TAVI has been growing lately, but at present few data are available on its impact on clinical outcome in large populations.4,11-13 In particular, we already identified moderate/severe PVL as an independent predictor of late mortality (>30 days up to 1 year) after TAVI in the first 663 patients enrolled in the Italian CoreValve Registry.4
Aim of the present study was to evaluate the incidence and predictors of moderate/severe PVL after CoreValve implantation, and to assess its impact on late mortality and left ventricular (LV) remodeling among patients discharged alive.
2
Methods
Patient population and study design. Between June 2007 and December 2010, 984
consecutive patients with symptomatic severe aortic stenosis underwent TAVI using the 18-Fr third-generation CoreValve bioprosthesis at 14 Italian hospitals. Details on patient selection and TAVI technique were previously described.4,14,15 The study was approved by the institutional Ethics Committees and all patients gave written informed consent. Patients who died in hospital (n=53), required conversion to emergency surgery (n=8), did not receive the prosthesis in the proper anatomical location (n=6), or did not have a complete echocardiographic assessment before discharge (n=54) were excluded from the study (Figure 1). Forty-two additional patients were lost at follow-up within 1 year of TAVI, so that the study population was composed of 821 patients. The primary end point was all-cause mortality occurring between hospital discharge and 1 year (late mortality).
Echocardiographic assessment. All patients included in the study had a complete transthoracic Doppler echocardiography (TTE) before TAVI and at time of hospital discharge. In order to assess the evolution of PVL and its impact on LV remodeling more accurately, we decided to include in the serial echocardiographic analysis only those centers with completeness of 1-year echocardiographic follow-up >70%. Thus, the echocardiographic changes at 1 year were evaluated in 327 out of 414 patients (79.0%) discharged alive from the 5 centers with higher follow-up completeness (Figure 1). Echocardiographic measurements were performed according to current recommendations.16 Post-operative aortic regurgitation was considered paravalvular if the regurgitation jet was identified as originating between the prosthetic valve frame and the native valve annulus. Paravalvular leak at hospital discharge was graded as absent or trivial (0), mild (1), moderate (2) and severe (3), according to the Valve Academic Research Consortium (VARC) criteria.17 We then divided patients into two groups: patients showing no/mild PVL (Group PVL<2), and patients showing moderate/severe PVL (Group PVL≥2). To evaluate the mismatch between the prosthesis and the aortic annulus, we calculated a TTE “cover index”,
3 defined as: ([prosthesis diameter -TTE annulus diameter]/prosthesis diameter) x 100, as
transesophageal echocardiography was not available in the majority of patients to calculate the “cover index” according to the original definition.6
Evaluation of prosthesis implantation level. To measure the depth of CoreValve implantation inside the LV outflow tract (LVOT), we chose the final angiographic projection showing the best lateral view of the CoreValve frame and measured the distance between the lower edge of the noncoronary aortic cusp and the ventricular end of the CoreValve frame, by means of the quantitative coronary angiographic analysis software locally available. We defined “low implantation” a level of prosthesis implantation below the aortic annulus >6 mm.18,19 Definitions. In October 2011, the information contained in the web-based registry were re-evaluated to assess the procedural results and clinical end points according to the VARC definitions.17 In particular, we assessed device success, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, vascular complications, and bleeding complications. Statistical analysis. Continuous variables were analyzed for a normal distribution with the Shapiro-Wilk test. Continuous variables following a normal distribution are presented as mean ± standard deviation and were compared using a Student’s unpaired t test for comparisons between groups and a Student’s paired t test for within-group comparisons. Variables not following a normal distribution are expressed as median (IQR), and were compared with a Mann-Whitney test for comparisons between groups and a Wilcoxon test for within-group comparisons. Categorical variables are presented as counts and percentages, and were compared using 2 or Fisher exact tests, as appropriate. Repeated-measures analysis of variance (ANOVA) was used to assess the influence of time and PVL≥2 on echocardiographic parameters. A
stepwise logistic regression analysis including all variables from Tables 1 and 2 with probability value <0.20 at univariate analysis was used to determine independent predictors of PVL≥2; results are presented as odds ratio (OR) with 95% confidence intervals (95%CI). A stepwise Cox multivariate analysis including all variables from Tables 1 and 2 with probability value
4 <0.20 at univariate analysis was used to determine independent predictors of late mortality. Results are presented as hazard ratio (HR) with 95%CI. The validity of the proportionality assumption was verified for all covariates by a visual examination of the log (minus log) curves and a test based on the Schoenfeld residuals. The cumulative incidences of clinical events at follow-up were assessed by using the Kaplan-Meier method, and the log-rank test was used for comparison between groups. All probability values reported are 2-sided, and a probability value <0.05 was considered significant. All data were processed using the Statistical Package for Social Sciences, version 19 (SPSS, Chicago, IL).
5 Results
Patient population. Baseline characteristics are detailed in Table 1. Median patient age was 83 years (79-86), with 377 men (45.9%), and a median logistic EuroSCORE of 20% (13-30%). At time of hospital discharge, 148 patients (18.0%) showed no PVL, 499 patients (60.8%) mild PVL, 161 patients (19.6%) moderate PVL, and 13 (1.6%) severe PVL. Therefore, 647 patients (78.8%) composed Group PVL<2, and 174 (21.2%) Group PVL≥2.
Predictors of moderate/severe PVL. The association between baseline clinical and echocardiographic characteristics and PVL≥2 at univariate analysis is reported in Table 1. Patients suffering from PVL≥2 were more often male (P=0.03), had larger aortic annulus diameter (P=0.001), larger LVOT diameter (P<0.0001), larger LV end-diastolic diameter (P<0.0001) and volume (P=0.0005), larger LV end-systolic diameter (P<0.0001) and volume (P=0.0009), and lower LV ejection fraction (P=0.007). The association between procedural and post-procedural data and PVL≥2 is reported in Table 2. Patients with PVL≥2 underwent low CoreValve implantation (P=0.01) and CoreValve postdilatation more frequently (P<0.0001), had a lower cover index (P=0.0007), and a lower LV ejection fraction (P=0.02). The rate of low CoreValve implantation was 19.2% among the first 26 patients treated in 2007, and ranged between 8.9% and 10.3% in the following years. At multivariate analysis, independent predictors of PVL≥2 were: larger LVOT diameter (OR 1.18, 95%CI 1.02-1.36; P=0.02), and low CoreValve implantation level (OR 2.34, 95%CI 1.08-5.07; P=0.03) (Table 3).
Predictors of late mortality. One-hundred and one patients died between 30 days of TAVI and 1-year follow-up (12.3%), 69 (10.6%) in Group PVL<2 vs. 32 (18.3%) in Group PVL≤2
(P=0.005) (Table 4). In particular, there were 21 cardiac deaths (3.2%) in Group PVL<2 vs. 15 (8.6%) in Group PVL≤2 (P=0.002). At univariate analysis, the baseline and periprocedural risk factors for late mortality were: PVL≥2 (P=0.005), NYHA class III-IV (P=0.01), diabetes (P=0.04), prior acute pulmonary edema (P=0.04), preoperative serum creatinine >2mg/dl (P=0.0001), higher logistic EuroSCORE (P=0.05), lower cover index (P=0.02), post-procedural
6 acute kidney injury-stage 3 (P=0.0005), life-threatening bleedings (P=0.05), and need for post-procedural blood transfusions (P=0.002). Multivariate analysis identified pre-post-procedural serum creatinine >2mg/dl (HR=2.71, 95%CI 1.44–4.34, P=0.005), post-procedural acute kidney injury-stage 3 (HR=3.36, 95%CI 1.65–6.83, P=0.0008), post-procedural blood transfusions (HR=1.74, 95%CI 1.12–2.71, P=0.01), and PVL≥2 (HR=1.67, 95%CI 1.07–2.62, P=0.02), as independent predictors of late mortality (Table 3).
Impact of PVL≥2 on late outcome. Between discharge and 1 year, the primary endpoint of all-cause mortality was reached in 10.6% (n=69) of Group PVL<2 and 18.3% (n=32) of Group PVL≥2 (log-rank P=0.005) (Table 4). Kaplan-Meier estimates of mortality indicate a continuous worsening of outcome in patients with PVL≥2 (Figure 2), with a 1-year survival of 81.6±2.9% vs. 89.3±1.2% in Group PVL<2.
Late cardiac mortality occurred in 3.2% (n=21) of Group PVL<2 and 8.6% (n=15) of Group PVL≥2 (log-rank P=0.001) (Table 4), with progressive divergence of the Kaplan-Meier curves during follow-up (Figure 3), and a 1-year freedom from cardiac death of 96.6±0.7% vs.
91.1±2.2% in Group PVL<2 vs. PVL≥2, respectively.
Re-hospitalization for cardiac causes was also more common in Group PVL≥2 (15.5% vs 6.9%; P=0.0003), as well as the need for reintervention on the aortic valve (2.3% vs 0.1%; P=0.001), either with a second TAVI (3 patients in Group PVL≥2 and 1 patient in Group PVL<2), or with surgical aortic valve replacement (1 patient in Group PVL≥2) (Table 4). Median time to
reintervention was 4 months (IQR 1-8 months). The cause of reintervention was prosthetic valve dysfunction in all cases, consisting in moderate-to-severe central aortic regurgitation in 3
patients, and mean transprosthetic gradient>20 mmHg in 2 cases.
Echocardiographic follow-up. Among the 327 patients included in the 1-year
echocardiographic analysis, 260 (79.6%) belonged to Group PVL<2, and 67 (20.4%) to Group PVL≥2. In Group PVL<2, PVL remained unvaried in 217 patients (83.5%), improved in 28 (11.0%), and worsened to moderate PVL in 15 (5.8%) (Figure 4). In Group PVL≥2, PVL
7 remained unvaried in 50 patients (74.6%), improved to mild in 15 (22.3%), and worsened to severe PVL in 2 (2.9%) (Figure 4). Overall, there was a significant decrease in the average degree of PVL at ANOVA (F ratio=8.00; P=0.005).
The changes in LV function and morphology are summarized in Table 5. At 1-year follow-up, LV ejection fraction significantly improved both in Group PVL<2 (P<0.0001) and in Group PVL≥2 (P=0.02), with a similar time-pattern at ANOVA (F-Ratio=0.05; P=0.82). On the other hand, LV mass index decreased significantly both in Group PVL<2 (P<0.0001) and in Group PVL≥2 (P=0.01), but we observed a trend to a more steep decrease in Group PVL<2
(F-Ratio=2.83; P=0.09). Regarding LV end-diastolic volume, we observed a significant decrease in Group PVL<2 (P=0.01), but not in Group PVL≥2 (P=0.67), with a different time-pattern at ANOVA (F-Ratio=3.82; P=0.05). Accordingly, LV end-diastolic diameter showed a trend to increase in Group PVL≥2 (P=0.12), while remaining constant in Group PVL<2 (P=0.32), with a significant difference in the time-pattern (F-Ratio=8.52; P=0.004). Finally, we observed a trend to a significant difference in the relative change in mean transprosthetic gradient from hospital discharge to 1-year follow-up (P=0.08), confirmed at ANOVA (F-Ratio=3.60; P=0.06); in fact, a trend to a slight increase in mean gradient was observed only in Group PVL≥2.
8 Discussion
The presence of PVL is a relatively common finding after surgical aortic valve replacement, ranging between 1% and 17%, being trivial or mild in the vast majority of cases.20-22 Post-surgical PVL has been reported to have a benign course,20,21 although the most recent study identified residual aortic regurgitation more than mild as an independent predictor of postoperative mortality.22 Currently, the problem of PVL is gaining interest with the advent and increasing use of TAVI, which has been demonstrated a higher incidence of PVL, compared with surgical valve replacement. In fact, as many as 65% to 94% of patients undergoing TAVI develop some degree of PVL, with either of the 2 prostheses currently available.12 The
regurgitation is usually trivial or mild in the majority of cases, with an incidence of moderate/severe PVL of 5% to 10% for the Edwards SAPIEN (Edwards Lifesciences, Irvine, California),5-7,11 and of 15% to 40% for the Medtronic CoreValve (Medtronic, Minneapolis, MN).4,5,8-10 In the present study, some degree of PVL was observed in 82.0% of patients, being moderate or severe in 21.2% of the population. Given the largely positive early and medium-term results of TAVI reported in the initial studies, PVL was generally considered by interventional cardiologists as an acceptable drawback of this procedure, possibly self-reducing during follow-up. Most recently, growing evidence is supporting the importance of PVL as a marker of increased mortality after TAVI,4,5,10-12 highlighting the need for a uniform definition of PVL. Therefore, in the present study PVL was graded according to the VARC definitions,17 although PVL assessment after TAVI remains difficult even for experienced operators, as it often consists of multiple, eccentric jets.
The present study examined the Italian CoreValve Registry, enrolling almost 1,000 consecutive patients, and included by study design only patients successfully implanted, discharged alive, and followed-up for at least 1 year. Our principle finding, in a large cohort of 821 patients, is that the presence of a more than mild PVL at time of hospital discharge is an independent
9 predictor of late mortality, and is associated with increased morbidity and impaired LV remodeling at 1-year follow-up.
Predictors of moderate/severe PVL. The mechanisms leading to the development of PVL after TAVI can be grouped into anatomical and procedural factors. The most evident of anatomical factors is the incomplete circumferential apposition of the prosthetic frame to the native aortic annulus, owing to the different shapes of the aortic annulus and to the amount and/or distribution of calcium, together with leaflet thickness.6,10,13 In particular, the self-expanding CoreValve has a supra-annular position of the valve leaflets, and can conform its proximal in-flow portion to the annulus shape; however, the more elliptical the annulus shape and the larger its area, the more the prosthesis fails to completely cover the valve orifice. In agreement with previous reports, we confirmed that PVL≥2 was more common in patients with larger aortic annulus diameter,6,8-10,12 and with lower cover index.6,10,11,13 As a large aortic annulus is more common in subjects with larger body surface area, PVL≥2 was also associated with male gender, as previously reported.6,9,10,12 In addition, we also found a significant association between PVL≥2 and larger LVOT diameter, as well as larger LV end-diastolic and end-systolic diameters and volumes. However, at multivariate analysis only LVOT diameter emerged among morphologic parameters as an independent predictor of PVL≥2 (OR 1.18, 95%CI 1.02-1.36 per 1 mm increase; P=0.02). A possible explanation for our finding is that for any given discrepancy between the circular nitinol frame and the irregularly shaped aortic annulus, a larger LVOT diameter may determine a lack of sealing between the LVOT muscular wall and the in-flow portion of the CoreValve frame, leading to greater PVL. Moreover, a larger LVOT makes correct positioning of the CoreValve more difficult, as the inadequate contact between the in-flow portion of the nitinol stent and the LVOT may favor proximal displacement of the prosthesis during deployment, with the entailing risk of PVL. The predictive role of LVOT and annulus diameters underlines the importance of having accurate measurement before intervention. In fact, unlike surgical valve replacement, TAVI does not allow direct
10 measurement of the aortic annulus and has a very limited choice of prosthesis sizes. Recently, the routine use of multislice computed tomography with three-dimensional imaging has improved evaluation of the aortic root anatomy, resulting in a better selection of properly-sized prostheses.23,24 Importantly, our population was treated when the larger 31mm CoreValve prosthesis size was not yet available, and the risk of undersizing the prosthesis in patients with a larger annulus was higher. In fact, some degree of prosthesis oversizing is currently recommended for the CoreValve to optimize the adherence of the device to the aortic annulus, although published data did not support a reduction in PVL with greater prosthesis oversizing.8,25
Among the procedural factors leading to PVL, the depth of device implantation has a major role, particularly for the CoreValve.8 In the present study, we demonstrated that a low CoreValve implantation (>6 mm below the level of the aortic annulus) is an independent predictor of PVL≥2. In case of low implantation, in fact, the “skirt” of pericardium sewn to the in-flow portion of the nitinol stent remains entirely below the aortic annulus, allowing blood to
regurgitate from the aorta into the LV through the holes of the uncovered portion of the stent. A learning curve is required to minimize the risk of low CoreValve implantation, as previously demonstrated by Détaint;6 however, in the Italian Registry the rate of low implantation remained constant between 9 and 10% from 2008 to 2010, after the very beginning of our experience in 2007. Postdilatation of the CoreValve was another procedural factor associated with PVL≥2 in the present study. However, this is clearly owed to the attempt to reduce a pre-existing
moderate/severe PVL observed immediately after CoreValve deployment. In fact, postdilatation with a balloon may be performed to further expand the prosthesis and try to reduce the PVL, particularly in heavily calcified valves. However, we cannot exclude that in some patients postdilatation may have worsened PVL by causing structural damage to the prosthetic valve.26
11 Impact of PVL on outcome. The occurrence of more than mild PVL after TAVI, although known from the very beginning of this procedure, has only recently been associated with both in-hospital,12 and late mortality.4,5,10,11 In particular, in the Placement of Aortic Transcatheter Valves (PARTNER) trial even mild PVL (observed in about 40% of patients) was associated with higher 2-year mortality.11 Our study is the first to assess the impact of PVL on late
mortality in a large population of CoreValve recipients; importantly, we identified PVL≥2 as the only independent predictor of late mortality among pre-procedural demographic and
echocardiographic characteristics. Moreover, we observed that patients with PVL≥2 required more frequently both re-hospitalization for cardiac causes, and reintervention on the aortic valve during follow-up, reinforcing the dismal impact of PVL on clinical outcome.
Evolution of PVL and impact on LV function and remodeling. Our serial echocardiographic analysis at 1 year in 327 patients offers a relevant contribution to the understanding of the consequences of PVL after TAVI. In fact, we describe the echocardiographic evolution of the largest population of CoreValve recipients with an echocardiographic follow-up completeness of 79%. Firstly, we observed a statistically significant, although mild, improvement in the average degree of PVL during follow-up (P=0.005), with improvement in 13.1% of patients, and worsening in 5.2%. At present, few data are available concerning the evolution of PVL after TAVI; some reduction in the rate of PVL≥2 at 1 to 3 years has been reported for both the CoreValve,27,28 and the Sapien,11,29 but no statistical analysis was specifically performed. Self-expansion of the nitinol frame and in-growth of tissue around the prosthetic valve might explain the reduction in PVL in our study; however, further investigations are warranted on PVL
evolution during follow-up and its predictors.
Secondly, we observed a significant improvement in LV ejection fraction at 1 year in both Groups, in agreement with previous reports.25,30,31. However, only Group PVL<2 showed a significant reduction in LV end-diastolic volume (P=0.01), with a different evolution during follow-up compared with Group PVL≥2 for both LV end-diastolic volume (P=0.05) and
12 diameter (P=0.004). These findings are presumably related to the volume overload caused by the PVL. Accordingly, although the LV mass index decreased significantly in both groups, as previously described,30,31 a trend to a smaller reduction in Group PVL≥2 was observed (P=0.09). These findings demonstrate that the presence of a PVL≥2 after TAVI with the CoreValve
impacts negatively on LV remodeling, possibly explaining the higher cardiac morbidity and mortality observed during follow-up.
13 Study limitations. The Italian CoreValve registry is a multicenter, prospective registry with independent monitoring and event adjudication; however data are self-reported and have not been systematically validated. In addition, the present study excluded by design patients who died in-hospital, and those without echocardiographic assessment before discharge (12% of the entire registry population), thus potentially underestimating the rates of PVL≥2. Finally, the echocardiographic assessment was not performed by a core lab; however, all exams were performed by experienced physicians according to uniform criteria.
14 Conclusions
The presence of a post-procedural moderate or severe PVL was an independent predictor of late mortality and morbidity after TAVI with the CoreValve. In addition, moderate or severe PVL also impaired the favorable LV remodeling that occurs after TAVI. The presence of a large LVOT and a low implantation level of the prosthesis were the independent predictors of PVL≥2. These results warrant great care in trying to minimize PVL in CoreValve recipients, by means of accurate aortic valve sizing and prosthesis deployment. However, future iterations in prosthesis design need to address the issue of PVL.
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21 Figure Legends
Figure 1. Study population.echo denotes echocardiographic exam. Categorization in either group was made based on paravalvular leak at time of hospital discharge .
Figure 2. Kaplan-Meier estimates of mortality. PVL denotes paravalvular leak. Event-rates were compared using the log-rank test.
Figure 3. Kaplan-Meier estimates of cardiovascular mortality. PVL denotes paravalvular leak. Event-rates were compared using the log-rank test.
Figure 4. Evolution of paravalvular leak. Percentage of patients with various grades of paravalvular leak for both groups. PVL denotes paravalvular leak. Data refer to 327 patients who had a complete echocardiographic evaluation at 1 year.
22 Figure 1.
23 Figure 2.
24 Figure 3.
25 Figure 4.
26 Table 1. Baseline clinical and echocardiographic profile, according to PVL at discharge.*
All patients (n=821) PVL<2 (n=647) PVL≥2 (n=174) P value Age, years 83 (79-86) 83 (79-86) 83 (78-86) 0.92 Male gender 377 (45.9) 285 (44.1) 92 (52.8) 0.03 Logistic EuroSCORE† 20 (13-30) 20 (13-30) 21 (13-32) 0.48
NYHA functional class III/IV 562 (68.4) 446 (68.9) 116 (66.6) 0.56
Diabetes mellitus 230 (28.0) 186 (28.7) 44 (25.2) 0.36
Coronary artery disease 414 (50.4) 324 (50.1) 90 (51.7) 0.69 Prior myocardial infarction 163 (19.8) 127 (19.6) 36 (20.6) 0.75 Prior acute pulmonary edema 174 (21.2) 107 (19.9) 67 (23.6) 0.22 Serum creatinine >2mg/dl 80 (9.8) 64 (10.0) 16 (9.1) 0.79 Aortic annulus diameter, mm 22 (21-24) 22 (21-24) 23 (22-24) 0.001 Aortic valve area index, cm2/m2 0.40 (0.30-0.54) 0.40 (0.30-0.54) 0.40 (0.30-0.52) 0.38 Mean aortic gradient, mmHg 50 (42-61) 50 (42-60) 51 (40-62) 0.77 LV outflow tract diameter, mm‡ 20.0±2.4 19.7±2.4 20.9±2.2 <0.0001 LV end-diastolic diameter, mm 50 (46-55) 49 (45-53) 52 (48-59) <0.0001 LV end-systolic diameter, mm 32 (27-38) 31 (27-37) 35 (30-44) <0.0001 LV end-diastolic volume, mL 100 (80-130) 99 (80-123) 111 (87-160) 0.0005 LV end-systolic volume, mL 45 (33-66) 44 (32-62) 55 (39-84) 0.0009 LV ejection fraction, % 51 (45-60) 55 (45-60) 52 (39-59) 0.007 Mitral valve regurgitation ≥2 311 (37.9) 240 (37.1) 71 (41.0) 0.34
*Results are presented as median (interquartile range) or absolute number (percentage), unless stated otherwise. PVL denotes paravalvular leak, NYHA New York Heart Association, LV left ventricular.
27 †The logistic EUROpean System for Cardiac Operative Risk Evaluation (EuroSCORE) is a score system used to predict 30-day mortality of cardiovascular surgery.
28 Table 2. Procedural results and post-procedural echocardiographic data, according to PVL at discharge.*
*Results are presented as median (interquartile range) or absolute number (percentage). PVL denotes paravalvular leak, LV left ventricular.
†Calculated with aortic annulus diameter measured at transthoracic echocardiography All patients (n=821) PVL<2 (n=647) PVL≥2 (n=174) P value Procedural data Non-transfemoral access 110 (13.3) 87 (13.4) 23 (13.2) 0.66 29mm CoreValve 355 (43.2) 273 (42.1) 82 (47.1) 0.24 CoreValve-in-CoreValve 34 (4.1) 26 (4.0) 8 (4.5) 0.73
Low CoreValve implantation 79 (9.6) 54 (8.3) 25 (14.3) 0.01 Cover Index, (%)† 17.4 (14.2-23.1) 19.2 (15.4-23.1) 16.7 (13.8-20.7) 0.0007 CoreValve postdilatation 101 (12.3) 61 (9.4) 40 (23.0) <0.0001 Post-procedural data
LV ejection fraction, % 55 (49-60) 55 (50-60) 55 (45-58) 0.02 Mean aortic gradient, mmHg 9 (6-12) 9 (6-12) 10 (7-13) 0.09 Aortic valve area index, cm2/m2 1.75 (1.40-2.20) 1.66 (1.40-2.20) 1.90 (1.50-2.31) 0.17
Acute kidney injury-stage 3 31 (5.0) 30 (4.6) 10 (5.7) 0.58
Blood transfusion≥1 unit 294 (35.8) 233 (36.0) 61 (35.1) 0.82
29 Table 3. Predictors of PVL≥2 and of late mortality at multivariate analysis.
PVL denotes paravalvular leak, CI 95% confidence interval, LV left ventricular.
PVL≥2 P value Odds Ratio 95%CI
LV outflow tract diameter, mm 0.02 1.18 1.02-1.36
Low CoreValve implantation 0.03 2.34 1.08-5.07
Cover Index, % 0.19 0.94 0.85-1.03
Late mortality P value Hazard Ratio 95%CI
Pre-procedural serum creatinine >2mg/dl 0.005 2.71 1.44–4.34 Post-procedural acute kidney injury-stage 3 0.0008 3.36 1.65–6.83
Blood transfusion≥1 unit 0.01 1.74 1.12–2.71
30 Table 4. Clinical outcomes at 1-year follow-up.
PVL denotes paravalvular leak
†1 case of CoreValve-in-CoreValve implantation
‡3 cases of CoreValve-in-CoreValve implantation and 1 surgical aortic valve replacement. All patients (n=821) PVL<2 (n=647) PVL≥2 (n=174) P value All-cause death 101 (12.3) 69 (10.6) 32 (18.3) 0.005 Cardiac death 36 (4.4) 21 (3.2) 15 (8.6) 0.002 Cardiac rehospitalization 72 (8.7) 45 (6.9) 27 (15.5) 0.0003 Stroke 19 (2.3) 13 (2.0) 6 (3.4) 0.26 Myocardial infarction 9 (1.1) 7 (1.1) 2 (1.1) 0.93
Aortic valve reintervention 5 (0.6) 1 (0.1)† 4 (2.3)‡ 0.001
31 Table 5. Comparison of Doppler echocardiographic data at baseline and at 1-year follow-up within and between Groups.
PVL<2 (n=260) PVL≥2 (n=67) P value LV ejection fraction, % Baseline 55(47-60) 53(39-58) 0.04 1 year 57(51-61) 53(48-60) 0.006
P value (1 year vs. baseline) <0.0001 0.02
Absolute change (1 year - baseline)† 3±10 3±12 0.78
LV end-diastolic volume, ml
Baseline 97 (78-125) 110 (78-164) 0.05
follow-up 90 (73-110) 116 (3-147) <0.0001
P value (1 year vs. baseline) 0.01 0.67
Absolute change (1 year - baseline)† -6±35 4±40 0.13
LV end-diastolic diameter, mm
Discharge 50 (46-54) 52 (47-59) 0.07
follow-up 50 (46-54) 56 (51-60) <0.0001
P value (1 year vs. baseline) 0.32 0.12
Absolute change (1 year - baseline)† -1±6 1±6 0.07
LV mass index, g/m2
Baseline 143 (127-170) 153 (121-180) 0.39
1 year 125 (109-149) 138 (117-165) 0.008
P value (1 year vs. baseline) <0.0001 0.01
32 Mean transprosthetic gradient, mmHg
Hospital discharge 9(7-12) 10(7-13) 0.40
follow-up 9(6-11) 10(8-13) 0.004
P value (1 year vs. discharge) 0.33 0.21
Absolute change (1 year - discharge)† 0±4 1±5 0.10
*Results are presented as median (interquartile range) or absolute number (percentage), unless stated otherwise. PVL denotes paravalvular leak, LV left ventricular.
†Results presented as mean±SD.
