1. No category

Valvular and Congenital Heart Disease
Trends in outcome after transfemoral transcatheter
aortic valve implantation
Nicolas M. Van Mieghem, MD, a Alaide Chieffo, MD, b Nicolas Dumonteil, MD, c Didier Tchetche, MD, d
Robert M. A. van der Boon, MSc, a Gill L. Buchanan, MBChB, b Bertrand Marcheix, MD, PhD, c Olivier Vahdat, MD, d
Patrick W. Serruys, MD, PhD, a Jean Fajadet, MD, d Didier Carrié, MD, PhD, c Antonio Colombo, MD, PhD, b
and Peter P. T. de Jaegere, MD, PhD a Rotterdam, The Netherlands; Milan, Italy; and Toulouse, France
Background Transfemoral transcatheter aortic valve implantation (TF-TAVI) is a viable and safe treatment strategy
for patients with symptomatic severe aortic stenosis and high operative risk and has been introduced as such in the
recently updated European guidelines on the management of valvular heart disease.Our aim was to assess trends in
outcome after TF-TAVI.
Methods
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DR
Propensity score–matched analysis of a multicenter registry of consecutive patients undergoing TF-TAVI
subdivided into 3 tertiles based on enrollment date was performed. Three tertiles of 214 propensity score–matched patients
were compared.
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Results With mounting experience and moving from the initial to the last cohort, procedural contrast volume and
radiation time decreased. Over time, there were less major vascular complications (15% vs 7.9%, P = .023), lifethreatening bleedings (17.8% vs 7.9%, P = .003), and major bleedings (22.4% vs 12.1%, P = .007). Major vascular
complications and life-threatening bleedings caused by closure device failure decreased significantly (9.2% vs 3.1% [P =
.01] and 5.7% vs 1 % [P = .01], respectively). The combined safety end point dropped from 31.3% in tertile (T) (T1) to
17.8% in T3 (P b .001). By multivariable analysis, the last cohort as compared with the initial cohort was associated with
significant reductions in 30-day mortality (odds ratio [OR] 0.35, 95% CI 0.12-0.96), stage 3 AKI (OR 0.12, 95% CI
0.29-0.93), and the combined safety end point (OR 0.52, 95% CI 0.29-0.93). One-year survival improved significantly
(T1 79% vs T3 86%, P = .016).
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Conclusions Over time, TAVI is performed with significant reductions in major vascular complications, life-threatening
bleedings, and the combined clinical safety end point and improved 1-year survival. (Am Heart J 2013;165:183-92.)
Co
Since its clinical introduction in 2002, transcatheter
aortic valve implantation (TAVI) has transformed into a
viable and safe treatment strategy for patients with
symptomatic severe aortic stenosis (AS) and high
operative risk and has been introduced as such in the
recently updated European guidelines on the management of valvular heart disease. 1,2 The technology has
progressed from a transvenous antegrade approach into a
transarterial retrograde or transapical procedure. 3,4 Up to
now, most large multicenter registries have reported
TAVI data mainly reflecting the early experience. 5–10 The
From the aDepartment of Interventional Cardiology, Thoraxcenter, Erasmus Medical
Center, Rotterdam, The Netherlands, bSan Raffaele Scientific Institute, Milan, Italy, cHôpital
Rangueil, Toulouse, France, and dClinique Pasteur, Toulouse, France.
Submitted September 15, 2012; accepted November 16, 2012.
Reprint requests: Nicolas M. Van Mieghem, MD, Department of Interventional Cardiology,
Thoraxcenter, Erasmus MC, Rm Bd 171, 'sGravendijkwal 230 3015 CE, Rotterdam, The
Netherlands.
E-mail: [email protected]
0002-8703/$ - see front matter
© 2013, Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ahj.2012.11.002
randomized Placement of Aortic Transcatheter Valves
(PARTNER) trial enrolled patients with AS who had a
prohibitive (cohort B) or high operative risk (cohort A) in
participating centers with only limited experience with
the TAVI procedure. 11,12 The latter may have had an
impact on the final results, particularly in the PARTNER
cohort A, which randomized patients to either the
routine procedure of surgical aortic valve replacement
(SAVR) or TAVI. Notwithstanding this manifest lack of
TAVI experience, TAVI dramatically improved survival in
inoperable patients and was noninferior to SAVR in highrisk patients.
Mounting clinical experience and refinement of
device platforms and procedural technique may improve clinical end points. So far, this has not been
clearly demonstrated. Therefore, the aim of this study is
to evaluate trends in TAVI outcome as a surrogate for
the combined effect of experience and technological
refinements by assessing 3 consecutive propensity
score–matched cohorts from the large Pooled-RotterdAm-Milano-Toulouse In Collaboration Plus (PRAGMATIC Plus) initiative.
04/04/2014
American Heart Journal
February 2013
184 Van Mieghem et al
Table I. Baseline characteristics
P
Overall (n = 793) Tertile 1 (n = 264) Tertile 2 (n = 264) Tertile 3 (n = 265)
81.2 ± 7.0
419/793 (52.8)
26.10 ± 4.53
20.0 (12.3-27.7)
6.7 (3.5-9.9)
121/793 (15.3)
129/793 (16.3)
167/793 (21.1)
229/793 (28.9)
345/793 (43.5)
223/793 (28.1)
484/791 (61.0)
257/793 (32.4)
140/789 (17.7)
85/793 (10.7)
135/793 (17.0)
0.70 ± 0.19
80.9 ± 6.3
145/264 (54.9)
26.13 ± 4.16
21.5 (14.1-29.0)
7.0 (3.7-10.2)
41/264 (15.5)
48/264 (18.2)
69/264 (26.1)
82/264 (31.1)
132/264 (50.0)
81/264 (30.7)
170/263 (64.6)
104/264 (39.4)
39/263 (14.8)
26/263 (9.8)
48/264 (18.2)
0.66 ± 0.17
81.5 ± 7.5
142/265 (53.8)
26.40 ± 4.66
18.5 (11.2-25.8)
5.6 (2.8-8.3)
37/264 (14.0)
38/264 (14.4)
49/264 (18.6)
73/264 (27.7)
105/264 (39.8)
69/264 (26.1)
153/264 (58.0)
77/264 (29.2)
45/263 (17.1)
33/264 (12.5)
41/264 (15.5)
0.70 ± 0.19
81.2 ± 7.3
132/265 (49.8)
25.78 ± 4.74
20.1 (12.6-27.7)
7.9 (4.3-11.6)
43/265 (16.2)
43/265 (16.2)
49/265 (18.5)
74/265 (27.9)
108/265 (40.8)
73/265 (27.5)
161/264 (61.0)
76/265 (28.7)
56/263 (21.3)
26/265 (9.8)
46/265 (17.4)
0.75 ± 0.21
.63
.47
.29
.019
b.001
.77
.50
.04
.63
.033
.49
.29
.01
.14
.52
.71
b.001
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Age (y), mean ± SD
Male, n (%)
Body mass index (kg/m 2), mean ± SD
Logistic EuroSCORE, median (IQR)
STS score, median (IQR)
Previous cerebrovascular accident, n (%)
Previous myocardial infarction, n (%)
Previous coronary bypass graft, n (%)
Previous percutaneous coronary intervention, n (%)
Coronary artery disease, n (%)
Diabetes mellitus, n (%)
Glomerular filtration rate b60 mL/min, n (%)
Chronic obstructive pulmonary disease, n (%)
Peripheral vascular disease, n (%)
Permanent pacemaker, n (%)
Left ventricular ejection fraction ±35%, n (%)
Aortic valve area (cm 2), mean ± SD
Baseline characteristics of the unmatched cohort subcategorized according to timing enrollment date into 3 tertiles.
Study population
The PRAGMATIC Plus initiative is a collaboration of 4
European institutions with established TAVI experience.
Baseline patient characteristics, procedural details, and clinical
outcome data from a series of 944 consecutive patients who
underwent TAVI were collected, since the introduction of the
respective local TAVI programs until August 2011 (total time
span November 2005–August 2011): (1) San Raffaele Scientific
Institute, Milan (n = 330); (2) Clinique Pasteur, Toulouse (n =
224); (3) Thoraxcenter, Erasmus Medical Center, Rotterdam (n
= 206); and (4) Hôpital Rangueil, Toulouse (n = 184). The
number of operators per center remained comparatively stable
throughout the study period. Clinical end points were defined
and collected using the Valve Academic Research Consortium
(VARC) consensus definitions and pooled into a dedicated
multicenter database. 13,14
The combined safety end point at 30 days contained allcause mortality, major stroke, life-threatening/disabling bleeding, acute kidney injury (AKI) stage 3, periprocedural
myocardial infarction, major vascular complication, and repeat
procedure for valve-related dysfunction. Device success (VARC
definition) was defined as successful vascular access, delivery
and deployment of the device, and successful retrieval of the
delivery system with good performance of the prosthetic
heart valve (aortic valve area N1.2 cm 2, mean aortic valve
gradient b20 mm Hg or peak velocity b3 m/s, and aortic
regurgitation [AR] b 2) and only 1 valve implanted in the
proper anatomical location.
All 793 patients who underwent transfemoral TAVI, either
surgical or percutaneous, were eligible for this study: per
participating center, the patients were subdivided into equal
tertiles based on TAVI enrollment date; this generated 4 sets of
tertiles, which were then pooled to create 3 “consecutive”
cohorts (T1 = 264 patients, T2 = 264 patients, T3 = 265
patients). Baseline patient characteristics per cohort are shown
in Table I.
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Methods
Patient eligibility for the TAVI procedure in each center has
been described earlier and is comparable across the 4
centers. 15-17 Briefly, all patients with symptomatic severe AS
who underwent TAVI had been judged to be at high operative
risk by multidisciplinary heart team consensus (consisting of at
least 1 interventional cardiologist and 1 cardiothoracic
surgeon), based on clinical judgment, calculated risk scores
(Society of Thoracic Surgeons [STS], Logistic EuroSCORE), and
the interpretation of other risk variables not captured by the
established risk models.
Propensity-matched analysis
To achieve balance in baseline risk between the cohorts,
we used propensity score matching based on a nonparsimonious multivariable logistic regression model including the
following baseline variables: age, gender, body mass index,
previous stroke, previous myocardial infarction, previous
coronary artery bypass grafting, previous percutaneous
coronary intervention, diabetes, renal insufficiency, chronic
obstructive pulmonary disease, peripheral arterial disease, and
severe left ventricular dysfunction. Of note, device platform
or device size was not taken into consideration, given that
these technological refinements (eg, switch from Edwards
SAPIEN to SAPIEN XT, Edwards Lifesciences Inc., Irvine, CA)
specifically characterize the later tertiles. Matching was
performed intracenter, to account for inherent local practice
differences. Patients were matched according to the method
of nearest neighbor matching. 18 Each patient in the initial
tertile was assigned a random number. Starting with the
lowest number, the patient was matched with 1 patient from
the other 2 tertiles. A propensity score difference of ±0.05
(width 0.10) was used as a maximum caliper width for
patient matching. If no match was identified in the 3 tertiles,
the patient was excluded from further analysis. This process
was repeated for every patient within the respective centers
until all possible matches were formed. The matched patients
were then pooled in a unique database of 3 equally sized
cohorts of 214 patients (cohort 1 [T1], cohort 2 [T2], and
cohort 3 [T3]).
04/04/2014
American Heart Journal
Volume 165, Number 2
Van Mieghem et al 185
Table II. Baseline characteristics of the 3 patient cohorts after matching
Overall (n = 642) Tertile 1 (n = 214) Tertile 2 (n = 214) Tertile 3 (n = 214)
81.0 ± 7.1
327/642 (50.9)
26.31 ± 461
20.0 (12.2-27.8)
6.6 (3.5-9.6)
101/642 (15.7)
161/642 (15.7)
127/642 (19.8)
177/642 (27.6)
268/642 (36.9)
180/642 (28.0)
395/642 (61.5)
210/642 (32.7)
105/642 (16.4)
61/642 (9.5)
104/642 (16.2)
0.69 ± 0.20
80.7 ± 6.4
115/214 (53.6)
26.12 ± 4.20
21.0 (13.7-28.3)
7.0 (4.1-9.9)
33/214 (15.4)
38/214 (17.8)
49/214 (22.9)
64/214 (29.9)
102/214 (47.7)
66/214 (30.8)
139/214 (65.0)
82/214 (38.3)
30/214 (14.0)
17/214 (7.9)
38/214 (17.8)
0.66 ± 0.17
81.1 ± 7.7
106/214 (49.5)
26.71 ± 4.82
18.6 (11.2-26.0)
5.8 (2.5-9.0)
32/214 (15.0)
32/214 (15.0)
38/214 (17.8)
62/214 (29.0)
87/214 (40.7)
60/214 (28.0)
126/214 (58.9)
64/214 (29.9)
35/214 (16.4)
24/214 (11.2)
29/214 (13.6)
0.69 ± 0.20
81.1 ± 7.1
106/214 (49.5)
26.09 ± 4.77
20.1 (11.9-28.3)
6.7 (3.4-10.0)
36/214 (16.8)
31/214 (14.5)
40/214 (18.7)
51/214 (23.8)
79/214 (36.9)
54/214 (25.2)
130/214 (60.7)
64/214 (29.9)
40/214 (18.7)
20/214 (9.3)
37/214 (17.3)
0.75 ± 0.21
.80
.60
.29
.12
.11
.86
.60
.36
.32
.08
.43
.42
.10
.43
.51
.43
b.001
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Age (y), mean ± SD
Male, n (%)
Body mass index (kg/m 2), mean ± SD
Logistic EuroSCORE, median (IQR)
STS score, median (IQR)
Previous cerebrovascular accident, n (%)
Previous myocardial infarction, n (%)
Previous coronary bypass graft, n (%)
Previous percutaneous coronary intervention, n (%)
Coronary artery disease, n (%)
Diabetes mellitus, n (%)
Glomerular filtration rate b60 mL/min, n (%)
Chronic obstructive pulmonary disease, n (%)
Peripheral vascular disease, n (%)
Permanent pacemaker, n (%)
Left ventricular ejection fraction ±35%, n (%)
Aortic valve area (cm 2), mean ± SD
P
Results
After hospital discharge, mortality data were collected by
contacting the respective national civil registry, referring
physician, or general practitioner and were complete in 99.7%
of patients.
Patient and procedural characteristics
The overall study population had a high estimated
operative risk (median Logistic EuroSCORE 20% [IQR
12.3 %-27.7%] and median STS risk score 6.6% [IQR 3.5%9.6%]) without significant changes throughout the study
period apart from a higher prevalence of coronary artery
disease and chronic obstructive pulmonary disease in T1
(Table I). After the matching process, a total of 642
patients undergoing TAVI qualified for the final analysis
encompassing equal cohorts of 214 patients (Table II).
Overall, the mean age was 81.0 ± 7.1 years, and 51% were
male. The median Logistic EuroSCORE was 20.0% (IQR
12.2-27.8). Procedural details per cohort are illustrated in
Table III. The Medtronic CoreValve System (Medtronic
Inc., Minneapolis, MN) was used in 56.2% (361/642) of
cases, and the Edwards SAPIEN Valve was used in the
remaining cases. As for the Medtronic CoreValve System
procedures, larger inflow devices were more frequently
used in the later cohorts. The Edwards SAPIEN Valve
experience was characterized by the introduction of the
smaller profile SAPIEN XT platform, which is 18 or 19F
compatible, in the later 2 cohorts. The latest cohort
demonstrated significant reductions in the total amount of
contrast volume (115 mL vs 195 mL, P b .001) and
radiation time (19 minutes vs 25 minutes, P b .001).
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Statistical analysis
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Follow-up
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Categorical variables are presented as frequencies and
percentages and compared using Pearson χ 2 test (if
needed, Fisher exact test) or by testing for linear-by-linear
association, as appropriate for variables with more than 2
categories. Continuous variables are presented as means (±SD;
in case of a normal distribution) or medians (interquartile
range [IQR]; in case of a skewed distribution). Normality of the
distributions was assessed using the Shapiro-Wilks test. Oneway analysis of variance was used to compare means across
the respective cohorts; post hoc pairwise comparison was
done with Bonferonni correction. In case of a nonparametric
distribution or ordinal data, the Kruskal-Wallis analysis of
ranks was used; post hoc comparison was done using the
Mann-Whitney test with Bonferonni correction. Survival
analysis was performed by Kaplan-Meier test, with patients
being censored as of the last date known alive. Because the
arterial sheath size with the Edwards device changed over
the course of the study (the larger sizes were predominantly
used in the first cohort), additional univariable and multivariable Cox proportional hazards models—adjusting for all
baseline characteristics and arterial sheath size—comparing
the initial with the last cohort were used to assess the
impact of experience on the predefined 30-day clinical end
points and 1-year survival. A 2-sided α level of .05 was used
for all superiority testings. The statistical analyses were
performed using SPSS software version 17.0 (SPSS Inc,
Chicago, IL).
No extramural funding was used to support this work.The
authors are solely responsible for the design and conduct of
this study, all study analyses, the drafting and editing of the
manuscript, and its final contents.
Clinical end points
Overall, device success was 93.5%, with a trend toward
a lower frequency of postprocedural paravalvular AR ≥2.
The 30-day all-cause mortality was 6.1% (Table IV). The
incidence rates of major stroke, major vascular complications, life-threatening bleeding, stage 3 AKI, and need for
permanent pacemaker implantation were 2.2%, 11.5%,
13.2%, 4.4%, and 16.2%, respectively. The combined
safety end point was reached in 25.5% of patients.
04/04/2014
American Heart Journal
February 2013
186 Van Mieghem et al
Table III. Procedural details
Tertile 1
(n = 214)
Tertile 2
(n = 214)
Tertile 3
(n = 214)
P value for
trend over tertiles
106/642 (16.5)
251/642 (39.1)
4/642 (0.6)
104/642 (16.2)
177/642 (27.6)
51/214 (23.8)
63/214 (29.4)
0/214
39/214 (18.2)
61/214 (28.5)
30/214 (14.0)
98/214 (45.8)
0/214
28/214 (13.1)
58/214 (27.1)
25/214 (11.7)
90/214 (42.1)
4/214 (1.9)
37/214 (17.3)
58/214 (27.1)
.001
.008
.014
.79
.75
357/642 (55.6)
189/642 (29.4)
96/642 (15.0)
110/214 (51.4)
17/214 (7.9)
87/214 (40.7)
128/214 (59.8)
77/214 (36.0)
9/214 (4.2)
119/214 (55.6)
95/214 (44.4)
0/214
.38
b.001
b.001
Overall
(n = 642)
Procedural details
572/642 (89.1)
174/214 (81.3)
206/214 (96.3)
192/214 (89.7)
70/642 (10.9)
40/214 (18.7)
8/214 (3.7)
22/214 (10.3)
54/572 (9.4)
18/174 (10.3)
24/206 (11.7)
12/192 (6.3)
82/642 (12.8)
29/214 (13.6)
25/214 (11.7)
28/214 (13.1)
150.0 (99.8-200.3) 195.0 (128.0-262.0) 170.0 (118.0-222.0) 115.0 (85.0-145.0)
Radiation time (min), median (IQR) †
22.0 (16.0-28.0)
25.4 (19.0-31.8)
19.0 (13.7-24.3)
b.001
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ing outcome trends after transfemoral TAVI: (1) manifest
cutbacks in procedural radiation time and contrast
volume; (2) significant reductions in major vascular
complications, life-threatening bleeding complications,
and the combined safety end point; (3) clear trends
toward lower 30-day all-cause mortality, postprocedural
AR ≥2, and stage 3 AKI; and (4) improved 1-year survival.
Over time, the frequency of the major clinical end
points has dropped into the single-digit numbers and
compares favorably with what has been reported
before. 19-23 The Vancouver group compared the initial
half with the second half of their first 270 high-risk
patients with AS undergoing TAVI and found significant
improvements in device success with reductions in 30day mortality from 13.3% to 5.9% (P = .04) but no effect
on stroke, major vascular injury, or the need for N4 red
blood cell (RBC) transfusions. 24 These researchers also
documented a significant decline in femoral vascular
complications between the fiscal years 2009 and 2010
from 8% to 1%, with concomitant reductions in major
bleeding (from 14% to 1%), need for RBC transfusion
(from 22% to 7%) or unplanned surgery (from 28% to
2%), and hospital length of stay (from 7.7 to 6.8 days). 25
Data from the Munich Heart Center on 420 consecutive
patients undergoing TAVI demonstrated a shift over
time toward a selection of patients with a lower
operative risk for TAVI; this report subcategorized the
patients into 4 unmatched cohorts based on enrollment
date and showed no change in 30-day mortality. 26
Himbert et al 27 demonstrated—by multivariate analysis
adjusting for risk profile—higher implantation success
rates and reduced inhospital death rates with growing
TAVI experience.
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All-cause 30-day mortality trended to be lower in the last
cohort (7.0% in T1 vs 3.7% in T3, P = .16). The combined
safety end point dropped from 31.3% in the initial cohort to
17.8% in the last cohort (P b .001). With mounting
experience and moving from the initial to the last cohort,
there were significantly less major vascular complications
(15% vs 7.9%, P = .023), life-threatening bleedings (17.8% vs
7.9%, P = .003), and major bleedings (22.4% vs 12.1%, P =
.007) (Figure 1). Major vascular complications and lifethreatening bleedings caused by closure device failure
decreased significantly (9.2% vs 3.1% [P = .01] and 5.7% vs
1% [P = .01], respectively). The frequency of stage 3 AKI
trended to be lower. No differences were seen in the
frequencies of postprocedural myocardial infarction,
neurologic events, and need for permanent pacemaker
implantation. By multivariable analysis including adjustment for arterial sheath size, the last cohort as compared
with the initial cohort was associated with significant
reductions in 30-day mortality (odds ratio [OR] 0.35, 95%
CI 0.12-0.96), stage 3 AKI (OR 0.12, 95% CI 0.29-0.93), and
the combined safety end point (OR 0.52, 95% CI 0.29-0.93)
(Figure 2). The 1-year Kaplan-Meier survival curves for the
3 cohorts illustrate improved 1-year survival over time (T1
79% vs T2 85% and T3 86%, P = .016 for T1 vs T3);
conversely, cardiovascular mortality remained unchanged
(Figures 3 and 4). By multivariable analysis including
adjustment for arterial sheath size, experience (expressed
as last cohort vs initial cohort) was associated with better
1-year survival (hazard ratio 0.52, 95% CI 0.31-0.87).
21.9 (15.3-28.5)
.005
.005
.17
.83
b.001
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Procedural details in the 3 matched cohorts.
⁎ Data were available in 560 patients.
† Data were available in 459 patients.
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Prosthesis type and size, n (%)
Medtronic CoreValve 26 mm
Medtronic CoreValve 29 mm
Medtronic CoreValve 31 mm
Edwards SAPIEN 23 mm
Edwards SAPIEN 26 mm
Sheath size
18F Medtronic
18F-19F Edwards
N19F
Method of access site closure, n (%)
Closure device
Surgical closure
Closure device failure, n (%)
Postdilatation for AR, n (%)
Amount of contrast (mL),
median (IQR)⁎
Discussion
This propensity score–matched analysis from the
PRAGMATIC plus collaboration demonstrates the follow-
04/04/2014
American Heart Journal
Volume 165, Number 2
Van Mieghem et al 187
Table IV. Clinical end points in the 3 matched cohorts
Tertile 2
(n = 214)
Tertile 3
(n = 214)
P value for
trend over tertiles
600/642 (93.5)
116/627 (18.5)
1.74 ± 0.40
198/214 (92.5)
42/208 (20.2)
1.75 ± 0.48
200/214 (93.5)
46/210 (21.9)
1.76 ± 0.38
202/214 (94.4)
28/209 (13.4)
1.70 ± 0.34
.44
.07
.40
5/642 (0.8)
3/642 (0.5)
2/214 (0.9)
1/214 (0.5)
2/214 (0.9)
0/214
1/214 (0.5)
2/214 (0.9)
.58
.48
14/642 (2.2)
3/642 (0.5)
10/642 (1.6)
4/214 (1.9)
1/214 (0.5)
5/214 (2.3)
5/214 (2.3)
0/214
3/214 (1.4)
5/214 (2.3)
2/214 (0.9)
2/214 (0.9)
.74
.48
.24
74/642 (11.5)
81/642 (12.6)
32/214 (15.0)
31/214 (14.5)
25/214 (11.7)
28/214 (13.1)
17/214 (7.9)
22/214 (10.3)
.023
.19
35/572 (6.1)
31/572 (5.4)
16/174 (9.2)
10/174 (5.7)
13/206 (6.3)
14/206 (6.8)
6/192 (3.1)
7/192 (3.6)
.01
.36
85/642 (13.2)
126/642 (19.6)
63/642 (9.8)
38/214 (17.8)
48/214 (22.4)
23/214 (10.7)
30/214 (14.0)
52/214 (24.3)
15/214 (7.0)
17/214 (7.9)
26/214 (12.1)
25/214 (11.7)
.003
.007
.75
20/572 (3.5)
21/572 (3.7)
10/174 (5.7)
8/174 (4.6)
8/206 (3.9)
10/206 (4.9)
2/192 (1.0)
3/192 (1.6)
.01
.12
40/214 (18.7)
9/214 (4.2)
12/214 (5.6)
37/214 (17.3)
30/114 (26.3)
7/100 (7.0)
67/214 (31.3)
34/214 (15.9)
6/214 (2.8)
11/214 (5.1)
32/214 (15.0)
24/128 (18.8)
8/86 (9.3)
59/214 (27.6)
27/214 (12.6)
4/214 (1.9)
5/214 (2.3)
35/214 (16.4)
29/119 (24.4)
6/95 (6.3)
38/214 (17.8)
.09
.15
.09
.79
.74
.87
b.001
75/214 (7.0)
14/214 (6.5)
16/214 (7.5)
10/214 (4.7)
8/214 (3.7)
7/214 (3.3)
.16
.12
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101/642 (15.7)
19/642 (3.0)
28/642 (4.4)
104/642 (16.2)
83/361 (23.0)
21/281 (7.5)
164/642 (25.5)
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Tertile 1
(n = 214)
39/642 (6.1)
31/642 (4.8)
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Device success, n (%)
Paravalvular AR grade ±2, n (%)
Postprocedural aortic valve area (cm 2), mean ± SD
Myocardial infarction, n (%)
Periprocedural (b72 h)
Spontaneous (N72 h)
Cerebrovascular complication, n (%)
Major stroke
Minor stroke
Transient ischemic attack
Vascular complication, n (%)
Major
Minor
Vascular complication due to closure device, n (%)
Major
Minor
Bleeding complication, n (%)
Life threatening
Major
Minor
Bleeding complication due to closure device, n (%)
Life threatening
Major
AKI, n (%)
Stage I
Stage II
Stage III
Permanent pacemaker requirement, n (%)
Medtronic CoreValve
Edwards SAPIEN
Combined safety end point, n (%)
30-d or inhospital death, n (%)
All-cause
Cardiovascular cause
Overall
(n = 642)
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Thirty-day mortality, stroke, and myocardial infarction
All-cause 30-day mortality in our series was 3.7% in the
last cohort as compared with 3.8% in the last quartile of
the Munich Heart Center experience and 4.7% in the
second half of the transfemoral cohort in the Vancouver
series. 24,26 We could not detect any changes in periprocedural myocardial infarction or stroke. This can probably be explained by the inherent invasiveness of the TAVI
procedure including the use of large bore catheters, the
passage of the aorta, and instrumentation in the aortic
root. Furthermore, in the present experience, embolic
protection devices that may influence embolization of
calcified debris to the brain were not available. 28,29
Beneficial effects of experience and
technological refinements
In the latest cohort, we found a 57% relative risk
reduction (9.9% absolute risk) in life-threatening bleedings to 7.9% and a 47% relative risk reduction (7.1%
absolute risk) in major vascular complications to 7.9%.
A recent weighted meta-analysis on TAVI outcome
using the uniform VARC definitions on 3,519 patients
from 16 studies reported life-threatening bleedings and
vascular complications in 15.6% and 11.9% of cases. 30
The reduction in life-threatening bleedings over time
can be the result of more stringent RBC transfusion
policies and the reduction in vascular complications
with mounting experience. Our data identify less
bleedings and vascular complications caused by closure
device failure, which likely results from growing
experience in access and closure technique and
superior patient selection. Technological refinements
during the study period with the introduction of smaller
profile devices (in the Edwards cohort) will have
contributed to the overall reduction in vascular and
bleeding complications.
One-year survival in the matched cohorts improved
from 79% in the initial cohort to 86% in the last cohort.
These data compare with the 81.1% 1-year survival in
the transfemoral cohort from the SOURCE registry and
78.8% in the transfemoral cohort from PARTNER cohort
A. Of note in our series, cardiovascular mortality
remained unchanged, yet all-cause mortality dropped
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February 2013
188 Van Mieghem et al
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Figure 1
Major end points in the 3 matched cohorts. Blue represents major stroke; red, life-threatening bleeding; light blue, all-cause mortality; green, major
vascular complications; orange, stage 3 AKI; and purple, combined safety end point (all-cause mortality, major stroke, life-threatening/disabling
bleeding, AKI stage 3, periprocedural myocardial infarction, major vascular complication, and repeat procedure for valve-related dysfunction).
suggesting, that (1) the local heart teams may get more
proficient in identifying those patients who have a
reasonable overall life expectancy (excluding patients
with grim prognosis caused by advanced comorbidities)
and (2) longer-term patient follow-up after TAVI has
evolved resulting in a decline in noncardiovascular
death the first year post-TAVI.
In our series, we documented a 40% and 25% decline in
total contrast volume and radiation time respectively,
which may explain the clear trend toward less stage 3
AKI. These data correspond with exploratory findings
from the Mayo Clinic demonstrating significant decreases
in procedural times, radiation, and contrast volumes
throughout their initial experience. 31
04/04/2014
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Volume 165, Number 2
Van Mieghem et al 189
Figure 2
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Multivariable analysis adjusting for all baseline characteristics and arterial sheath size comparing the effect of the last cohort with the initial cohort
for major clinical end points. CSE, combined safety end point.
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Figure 3
Kaplan-Meier estimates of 1-year freedom from all-cause mortality in 3 consecutive propensity score–matched cohorts. Red represents cohort 1;
blue, cohort 2; and green, cohort 3.
Growing experience and technological refinements
can lead to practice changes in terms of patient selection,
procedural execution, postoperative management, and
patient follow-up. During the study period, the patient
selection process has changed with the installation of
dedicated multidisciplinary heart teams consisting of
interventional cardiologists, cardiac surgeons, cardiac
imaging specialists, anesthesiologists, and, sometimes,
geriatricians and neurologists. The surge of multimodality
imaging with the integration of multislice computed
tomography scans, echocardiography, and conventional
invasive angiography has provided unprecedented anatomical information refining access strategy selection. 32,33 In our series, this has resulted in a preference
for larger valve sizes in the later cohorts (despite the
matching for gender and body habitus) and a strong trend
toward a lower frequency of postprocedural paravalvular
AR ≥2.
It is difficult to determine what level of experience will
suffice to reach a satisfactory plateau in TAVI proficiency;
04/04/2014
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190 Van Mieghem et al
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Figure 4
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Kaplan-Meier estimates of 1-year freedom from cardiovascular mortality in 3 consecutive propensity score–matched cohorts. Red represents
cohort 1; blue, cohort 2; and green, cohort 3.
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simulator training, observation of (and participation in)
cases at experienced centers, and presence of proctors
with initial experience should precede the roll out of new
TAVI programs, which should then vouch for an optimal
balance of procedural volume within a given limited time
frame to obtain sufficient skill sets and comfort ability to
execute TAVI. The concept of a multidisciplinary heart
team for risk stratification and patient selection and
access to multimodality imaging seem essential cornerstones for successful TAVI programs. Of note, current
operative risk assessment models such as the Logistic
EuroSCORE and the STS risk score underperform in the
TAVI setting. Also, particular variables not included in
these established models (e.g. frailty, porcelain aorta,
hostile mediastinum) have emerged as important items to
consider in patient selection, yet were not included in
this analysis. Furthermore, it is necessary to document
TAVI outcome data using uniform definitions to allow for
comparability of outcome results and assessment of the
learning curve. Professional societies have developed
position statements on operator and institutional requirements for TAVI performance to help accommodate
the dispersion of the TAVI technology while preserving
its potential to be a viable, less invasive alternative to
SAVR. 34,35
Limitations
The PRAGMATIC plus collaboration is a retrospective
study of prospectively collected data. Several limitations
deserve mentioning: (1) the database relies on each
institution's accuracy of data collection; (2) clinical end
points were not adjudicated by an independent clinical
event committee and are therefore subjected to
potential reporting bias; (3) there was considerable
heterogeneity in TAVI practice across centers; (4)
potential important variables such as frailty and
porcelain aorta have not been uniformly defined and
could therefore not be included in this analysis; and (5)
during the time span of this study, transaxillary and
direct aortic access were only incidentally used. We
acknowledge that the introduction of more alternative
access options and the selection of the optimal access
strategy for TAVI represent another aspect of the
learning curve because it will allow for an even more
patient-tailored approach based not only on clinical but
also on anatomical data.
Conclusion
Growing experience, technological refinements, and
device iterations resulted in significant reductions in
major vascular complications, life-threatening bleedings,
and the combined safety end point and improved 1-year
survival. Over time, TAVI is becoming a safer treatment
option for patients with AS.
Disclosures
Drs Van Mieghem and de Jaegere are responsible for
the overall content of the manuscript. The other authors
04/04/2014
American Heart Journal
Volume 165, Number 2
Van Mieghem et al 191
have been contributing by completing the respective
local databases and editing and reviewing the manuscript.
There was no funding involved in this project.
Conflict of interest: Drs Tchetche and Dumonteil are
proctors for Edwards Lifesciences and Medtronic CoreValve. Drs Marcheix is a proctor for Edwards Lifesciences.
Dr de Jaegere is a proctor for Medtronic CoreValve.
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