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Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Balloon-Expandable Transcatheter Heart Valve
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 8, NO. 14, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2015.08.014
Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Balloon-Expandable Transcatheter Heart Valve A Single-Center Experience Oliver Husser, MD,* Costanza Pellegrini, MD,* Thorsten Kessler, MD,* Christof Burgdorf, MD,* Hannah Thaller,* N. Patrick Mayr, MD,y Ilka Ott, MD,* Albert M. Kasel, MD,* Heribert Schunkert, MD,*z Adnan Kastrati, MD,*z Christian Hengstenberg, MD*z
ABSTRACT OBJECTIVES Evaluation of 30-day outcomes after transcatheter aortic valve replacement (TAVR) with the novel balloon-expandable SAPIEN 3 (S3) transcatheter heart valve (THV) (Edwards Lifesciences, Irvine, California) emphasizing the updated Valve Academic Research Consortium (VARC-2) criteria. BACKGROUND Preliminary data on clinical performance with the S3 THV are promising. However, information regarding 30-day outcome is limited. METHODS A total of 250 consecutive patients undergoing transfemoral TAVR with the S3 THV at our center were enrolled, and outcomes according to VARC-2 criteria were analyzed at 30 days. RESULTS The mean age was 81.0 6.2 years, median logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) and Society of Thoracic Surgeons score were 12.1% and 4.4%, respectively. VARC-2–defined device success was achieved in 244 patients (97.6%); moderate paravalvular leakage developed in 5 patients (2.0%). One patient (0.4%) died of a noncardiac cause and 8 patients (3.2%) had a stroke. Life-threatening bleeding and major vascular complications occurred in 12 (4.8%) and 9 (3.6%) of the patients, respectively. From discharge to 30 days, 5 patients (2.0%) were hospitalized due to valve-related symptoms or worsening of heart failure. The VARC-2 composite early safety endpoint was observed in 25 patients (10.0%). Permanent pacemaker implantation rate at 30 days was 15.2%. Myocardial infarction, coronary obstruction requiring intervention, valve-related dysfunction, and endocarditis were not observed. CONCLUSIONS We found very good 30-day results using the novel S3 THV with a low rate of clinical events according to VARC-2 criteria. The S3 THV is associated with high procedural success and favorable early safety profile. The need for pacemaker implantations appears to be more frequent than with its predecessor. (J Am Coll Cardiol Intv 2015;8:1809–16) © 2015 by the American College of Cardiology Foundation.
From the *Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany; yDeutsches Herzzentrum München, Institut für Anästhesiologie, Technische Universität München, Munich, Germany; zDeutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK) e.V. (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. Dr. Husser received minor travel fees from Edwards Lifesciences. Dr. Kasel is a consultant and proctor for Edwards Lifesciences. Dr. Hengstenberg is a proctor for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 5, 2015; revised manuscript received August 7, 2015, accepted August 13, 2015.
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30-Day Outcome With New Balloon-Expandable Device
T
ranscatheter aortic valve replace-
analysis. Therefore, the final study population con-
ment (TAVR) has rapidly evolved
sisted of 250 patients. All cases were discussed by the
from a novel technology to the
multidisciplinary heart team, and consensus was
preferred treatment for patients with severe
achieved regarding the therapeutic strategy. TAVR
symptomatic aortic stenosis who cannot un-
was performed in a hybrid operating suite with pa-
Association
dergo conventional surgical aortic valve
tients under general anesthesia or conscious seda-
TAVR = transcatheter aortic
replacement (1) and has been shown to be
tion. All patients provided written informed consent
valve replacement
noninferior in high-risk patients (2). Large
for the procedure.
THV = transcatheter heart
clinical registries have consistently reported
valve
excellent
S3 = SAPIEN 3
complication rates (6).
ABBREVIATIONS AND ACRONYMS MSCT = Multislice computed tomography
NYHA = New York Heart
outcomes
VARC-2 = Valve Academic
(3–5)
and
decreased
discharge, and at the 30-day follow-up visit. Left
Although, in part, this decrease may be attributable to increasing operator experience, the evolution of TAVR with novel transcatheter heart valves (THVs) and further iterations of delivery systems to reduce periprocedural complications also play an important part. Periprocedural complications include paravalvular leakage, new permanent pacemaker implantations, thromboembolic events, bleeding, and vascular complications. The SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California)
is
a
novel
TOMOGRAPHY DATA ANALYSIS. Transthoracic echo-
cardiography was performed before TAVR, before
SEE PAGE 1817
Research Consortium
ECHOCARDIOGRAPHY AND MULTISLICE COMPUTED
balloon-expandable
THV
featuring a lower profile delivery system (Commander, Edwards Lifesciences) to reduce the risk of vascular injury as well as access site complications and allows for rapid and accurate positioning. Additionally, this device features a sealing cuff to reduce paravalvular regurgitation (7). The S3 THV received the CE mark in Germany in January 2014. To date, only small series (8–10) and 1 modest-sized multicenter trial (11) have assessed this novel device and clinical efficacy, and 30-day outcome is still unclear. The upcoming final results of the large-scale multi-
ventricular ejection fraction, mean transvalvular gradient, and paravalvular regurgitation were determined. Discharge echocardiographic data were available for 242 patients, and 30-day echocardiographic follow-up was available in 185 patients. Multislice computed tomography (MSCT) was performed as part of the standard pre-procedural screening protocol. Aortic annulus measurements were assessed in multiple plane reconstructions according to the guidelines of the Society of Cardiovascular Computed Tomography (14). In short, the area and perimeter of the virtual aortic annulus were obtained by direct planimetry. The minimal and maximal diameter were determined, and the effective diameter was calculated as the sum of the minimal and maximal diameter divided by 2. Calcification of the valvular apparatus was assessed at the height of the aortic cusps, annulus, and the left ventricular outflow tract and visually graded as none, mild, moderate, and severe. Dedicated U.S. Food and Drug Administration–approved software (OsiriX MD 3.9.4, Pixmeo, Switzerland) was used.
center PARTNER II Trial: Placement of Aortic Trans-
PROSTHESIS SIZE SELECTION AND PROCEDURE.
catheter Valves (12) are still eagerly awaited.
The technical features of the S3 THV have been
Here we report our single-center experience using
described elsewhere (7,11). The device is available in
the S3 THV, according to the updated standardized
23-, 26-, and 29-mm sizes. The dimensions of a
endpoint definitions issued by the Valve Academic
nominally expanded S3 THV and the manufacturer’s
Research Consortium (VARC-2) (13) with special
sizing recommendations are given in Online Table 1.
emphasis on the composite early safety endpoint at
The final decision on prosthesis size was left to the
30 days.
discretion of the physicians performing the procedure based on MSCT measurements and taking into ac-
METHODS
count other anatomic features such as the presence and distribution of calcification, eccentricity of the
PATIENT POPULATION. Between January 2014 and
aortic annulus, and also the patient anatomy in case
March 2015, 261 consecutive patients with severe
of borderline sizing ranges.
symptomatic aortic stenosis were treated with trans-
The percentage of oversizing according to area was
femoral TAVR using the S3 THV at the Department
calculated using the formula: (nominal prosthesis
of Cardiology, Deutsches Herzzentrum München,
dimension/patient anatomy 1) 100. The adher-
Munich,
ence to the manufacturer’s sizing guidelines by area
Germany.
Patients
treated
with
other
devices or requiring valve-in-valve procedures due to
was categorized as “undersized,” “within range,” and
degenerated bioprostheses were excluded from the
“oversized.” The implantation plane was identified
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30-Day Outcome With New Balloon-Expandable Device
using previously described techniques, by either
was used to compare the proportions of patients in
calculation from the MSCT (15) or the combination of
New York Heart Association (NYHA) functional class
angiographic and fluoroscopic guidance (16). A pigtail
III/IV at baseline and 30 days. A 2-sided p value <0.05
was placed in the right coronary cusp, and an
was considered statistically significant for all anal-
orthogonal view of the 3 aortic cusps was confirmed
yses. IBM SPSS Statistics version 22 (IBM, Armonk,
by aortic angiography. Initially, the center dot was
New York) was used for all analyses.
placed at the middle of the virtual annulus, and the valve was expanded under rapid pacing. With
RESULTS
growing experience, to avoid excessively deep implantation of the prosthesis within the left ventricular
PATIENT CHARACTERISTICS. In total, 250 patients
outflow tract, this strategy was changed to a higher
undergoing transfemoral TAVR with the S3 THV were
position of the center dot in relation to the virtual
analyzed. Their mean age was 81.0 6.2 years, and
annulus plane.
43.6% were female. Baseline characteristics of the paravalvular
entire patient population are listed in Table 1. The risk
leakage was evident on post-deployment angiog-
profile included an elevated burden of comorbidities
raphy and/or transesophageal echocardiography or if
resulting in an intermediate-risk population (median
fluoroscopy
underexpansion
logistic EuroSCORE [European System for Cardiac
using the delivery system’s balloon and adding w1 to
Operative Risk Evaluation] I: 12.1%, EuroSCORE II:
2 ml to the recommended filling volume at the
4.2%, and Society of Thoracic Surgeons score: 4.4%).
operator’s discretion.
Left
Post-dilation
DEFINITION
was
revealed
OF
performed
prosthesis
ENDPOINTS
if
AND
ventricular
ejection
fraction
was
severely
FOLLOW-UP.
All data up to 30 days were prospectively collected during routine ambulatory visits at the outpatient clinic, by referring to the treating physician, and other hospital documentation or the patient directly. All clinical endpoints, procedural success, and the
T A B L E 1 Baseline Characteristics: Total Patients (N ¼ 250)
Clinical characteristics Age, yrs
81.0 6.2
Female
109 (43.6)
BMI, kg/m2
26.9 4.8
composite early safety endpoint at 30 days were
Logistic EuroSCORE I, %
categorized using VARC-2 criteria (13). In brief, device
EuroSCORE II, %
4.2 (2.6-7.4)
success was defined as the absence of procedural
STS score, %
4.4 (2.7-7.0)
mortality, correct positioning of a single prosthetic
NYHA functional class III/IV
heart valve in the proper anatomic location, and
COPD
31 (12.4)
Diabetes mellitus
72 (28.8)
intended performance. The occurrence of all-cause mortality, stroke, rehospitalization for worsening heart failure, vascular complications, bleeding, acute
GFR ml/min
12.1 (7.6-20.0)
167 (66.8)
52.4 22.1
Extracardiac arteriopathy
70 (28.0)
Peripheral vascular disease
36 (14.4)
kidney injury, myocardial infarction, valve-related
Previous stroke, major/minor
23 (9.2)
dysfunction, and endocarditis or valve thrombosis
Previous pacemaker
24 (9.6)
up to 30 days was assessed. The incidence of per-
Coronary artery disease
manent pacemaker implantation was recorded. The
Previous myocardial infarction
composite endpoint early safety at 30 days (all-cause
Previous PCI
mortality, stroke [disabling and nondisabling], lifethreatening bleeding, acute kidney injury (RIFLE [Risk, Injury, Failure, Loss, and End-stage kidney disease] 2 or 3 or renal replacement therapy), coronary artery obstruction requiring intervention, major
Previous CABG
170 (68.0) 23 (9.2) 102 (40.8) 15 (6.0)
Echocardiographic characteristics LVEF <35%
31 (12.4)
AR IIIþ
3 (1.2)
MR IIIþ
8 (3.2)
Electrocardiographic characteristics
vascular complication, and valve-related dysfunction
Atrial fibrillation
requiring repeat procedure) was evaluated.
RBBB
19 (7.6)
LBBB
7 (2.8)
75 (30.0)
STATISTICAL ANALYSIS. Continuous variables are
expressed as mean with the SD or the median with the interquartile range. A repeated-measures analysis of variance with the post hoc Bonferroni correction was used for within-patient repeated measures of mean transaortic gradient at baseline, after TAVR and at 30 days. McNemar test for correlated categorical data
Values are mean SD, n (%), or median (interquartile range). AR ¼ aortic regurgitation; BMI ¼ body mass index; CABG ¼ coronary artery bypass graft; COPD ¼ chronic obstructive pulmonary disease; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation GFR ¼ glomerular filtration rate; LBBB ¼ left bundle branch block; LVEF ¼ left ventricular ejection fraction; MR ¼ mitral regurgitation; NYHA ¼ New York Heart Association; PCI ¼ percutaneous coronary intervention; RBBB ¼ right bundle branch block; STS ¼ Society of Thoracic Surgeons.
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30-Day Outcome With New Balloon-Expandable Device
depressed (<35%) in 12.4% (31 of 250) of the patients. A previous pacemaker was present in 9.6% (24 of 250) of the patients. The median stay in the intensive care unit and the stay in hospital were 1.0 (1.0 to 2.0) and 5.0 (5.0 to 7.0) days, respectively. PROCEDURAL CHARACTERISTICS AND PROSTHESIS
T A B L E 3 MSCT-Derived Aortic Annular Anatomy and Degree of
Oversizing (N ¼ 248*)
Minimal diameter, mm
21.1 2.4
Maximal diameter, mm
27.1 2.7
Effective diameter, mm
24.1 2.4
Perimeter, mm
77.4 7.5
Area, cm2
SIZING. All patients underwent TAVR using the
Prosthesis oversizing by area, %
transfemoral access. Conscious sedation was used in
Eccentricity index
43.6% (109 of 250) of the patients. The 23-, 26-, and
Degree of calcification
4.7 0.9 7.2 (0.4 to 13.9) 0.2 0.1 (0–3)
29-mm S3 THVs were used in 42.8%, 37.2%, and
Cusps, moderate/severe
176 (70.4)
20.0% of the patients, respectively. Procedural char-
Annulus, moderate/severe
25 (10.0)
acteristics are shown in Table 2. MSCT measurements
LVOT, moderate/severe
of the aortic annulus are presented in Table 3. Measurements were evaluated for 248 patients because 1 patient did not undergo MSCT due to renal failure
17 (6.8)
Values are mean SD, median (interquartile range), or n (%). *Excluding patients without MSCT. LVOT ¼ left ventricular outflow tract; MSCT ¼ multislice computed tomography.
and 1 patient had not previously undergone MSCT. The mean aortic annular area was 4.7 0.9 cm 2,
56.4%, and it was mild in 41.6% and moderate in 2.0%
resulting in a median prosthesis oversizing by area of
of patients. No patient had severe paravalvular
7.2% (interquartile range: 0.4% to 13.9%). Prosthesis
leakage. Intended prosthesis performance was not
sizing was within the manufacturer’s recommended
achieved in 5 patients (2.0%) due to residual para-
range in 77.4%, undersized in 12.1%, and oversized in
valvular leakage more than grade II, and 1 patient
10.5% of the patients. Post-dilation was performed in
required a second valve due to severe paravalvular
34.4% (86 of 250).
leakage after the first valve implantation.
VARC-2–DEFINED DEVICE SUCCESS AND IN-HOSPITAL OUTCOME. VARC-2–defined
device
success
was
achieved in 97.6% (244 of 250) of the patients (Table 4). No intraprocedural death occurred. There was no post-implantation paravalvular leakage in
In-hospital outcome and complications are given in Table 5. No in-hospital death occurred. The stroke rate was 2.8% (7 of 250), with disabling strokes in 3 patients. Life-threatening bleeding and major vascular complications occurred in 4.4% (11 of 250) and 3.6% (9 of 250) of the patients, respectively. A new permanent pacemaker implantation was required in 35 patients (14.0%). Excluding patients with
T A B L E 2 Procedural Characteristics: Total Patients (N ¼ 250)
a permanent pacemaker at baseline, the incidence of
Prosthesis size, mm
new pacemaker implantation was 15.5% (25 of 226).
23
107 (42.8)
No myocardial infarction occurred. Acute kidney
26
93 (37.2)
injury (defined as RIFLE 2/3) occurred in 2.0%
29
50 (20.0)
(5 of 250). Postprocedural echocardiography showed a
Conscious sedation
109 (43.6)
ECMO Prophylactic Emergency Pre-dilation Standard balloon*
2 (0.8)
(43.3 15.2 mm Hg to 12.1 5.1 mm Hg; p < 0.0001)
1 (0.4)
(Figure 1).
246 (98.4) 175 (70.0)
Other balloon
71 (28.4)
Post-dilation†
86 (34.4)
Procedural time, min
59.9 22.9
Fluoroscopy time, min
13.4 5.7
Contrast, ml
113.9 62.6
Days in hospital
5.0 (5.0–7.0)
Days in the intensive care unit
1.0 (1.0–2.0)
Values are n (%), mean SD, or median (interquartile range). *Balloon with the recommended volume included with the delivery system and transcatheter heart valve (THV) (i.e., 20-mm balloon for 23-mm THV, 23-mm for 26-mm THV, and 25-mm for 29 mm-THV). †Post-dilation was performed using the delivery system’s balloon and adding w1 to 2 ml to the recommended filling volume at the operator’s discretion. ECMO ¼ extracorporeal membrane oxygenation.
significant decrease in mean transvalvular gradient
T A B L E 4 VARC-2–Defined Device Success (N ¼ 250)
Device success Procedural mortality Intended performance* Multiple valves
244 (97.6) 0 (0) 245 (98.0) 1 (0.4)
Correct position of the device in the proper anatomical location
250 (100)
Successful vascular access, delivery, and deployment of the device and successful retrieval of the delivery system
249 (99.6)
Values are n (%). *No prosthesis mismatch, mean aortic valve gradient <20 mm Hg or peak velocity <3 m/s, without moderate or severe prosthetic valve aortic regurgitation.
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30-Day Outcome With New Balloon-Expandable Device
T A B L E 5 Clinical Outcome In-Hospital and at 30 Days
In-Hospital Events (N ¼ 250)
F I G U R E 1 Mean Transvalvular Gradient at Baseline, Discharge, and 30 Days
At 30 Days* (N ¼ 250)
Mortality All-cause mortality
0 (0)
Noncardiac mortality
0 (0)
1 (0.4) 1 (0.4)
Cardiac mortality
0 (0)
0 (0)
All stroke
7 (2.8)
8 (3.2)
Disabling stroke
3 (1.2)
4 (1.6)
Nondisabling stroke
4 (1.6)
4 (1.6)
TIA
1 (0.4)
1 (0.4)
—
5 (2.0)
Neurological complications
Hospitalization for valve-related symptoms or worsened CHF Major vascular complication
9 (3.6)
9 (3.6)
Life-threatening bleeding
11 (4.4)
12 (4.8)
AKI 2/3, including renal replacement therapy
5 (2.0)
5 (2.0)
Coronary artery obstruction requiring intervention
0 (0)
0 (0)
Myocardial infarction
0 (0)
0 (0)
Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR)
0 (0)
0 (0)
Endocarditis
0 (0)
0 (0)
Valve thrombosis
0 (0)
NYHA functional class III/IV New pacemaker† VARC-2 early safety composite endpoint at 30 days
Mean transvalvular gradient at baseline, discharge, and 30 days in 185 patients with complete echocardiographic data showing a significant improvement in the mean transvalvular gradient after transcatheter aortic valve replacement and at 30 days.
0 (0)
—
17 (6.8)
proportion of patients in NYHA functional class III/IV
35 (14.0)
38 (15.2)
—
before and after TAVR (66.8% [167 of 250] vs. 6.8% [17
25 (10.0)
of 250]; p < 0.001). Of the patients who were hospitalized for worsening heart failure within 30 days
Values are n (%). *Events after hospital discharge until 30 days not available for 1 patient who was lost to follow-up due to inability to contact. †Percentage given for the entire cohort as the denominator; new pacemaker rate in hospital and at 30 days in patients without a previous pacemaker was 15.5% (35 of 226) and 16.8% (38 of 226), respectively.
(2.0%, 5 of 250), all showed NYHA functional class
AKI ¼ acute kidney injury; BAV ¼ balloon aortic valvuloplasty; CHF ¼ congestive heart failure; NYHA ¼ New York Heart Association; SAVR ¼ surgical aortic valve replacement; TAVR ¼ transcatheter aortic valve replacement; TIA ¼ transient ischemic attack; VARC ¼ Valve Academic Research Consortium.
gradient was stable from discharge examination to
lower than III at the 30-day visit. Echocardiographic data at 30 days were available for 185 patients. Mean
F I G U R E 2 NYHA Functional Class at Baseline and at 30 Ddays
VARC-2–DEFINED EARLY SAFETY AT 30 DAYS.
Follow-up at 30 days was complete in 249 patients. One patient was lost to follow-up due to inability to contact. The 30-day event-free rate was 90.0% (225 of 250), with the composite early safety endpoint observed in 10.0% (25 of 250) (Table 5). From hospital discharge to 30 days, 1 case of disabling stroke, 1 case of life-threatening bleeding, and 3 permanent pacemaker implantations were observed, resulting in a 30-day event rate of 3.2% (8 of 250), 4.8% (12 of 250), and 15.2% (38 of 250), respectively. No major vascular complication, myocardial infarction, endocarditis, or valve thrombosis was recorded from discharge to 30 days. One patient (0.4%) died of sepsis with multiorgan failure. Patients’ symptoms markedly ameliorated with an improvement in NYHA functional class in 89.2%
New York Heart Association (NYHA) functional class at baseline and discharge for
of the patients (Figure 2). Using the McNemar test,
250 patients with complete follow-up at 30 days.
there was a statistically significant difference in the
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30-Day Outcome With New Balloon-Expandable Device
30 days (12.1 5.1 mm Hg to 11.2 4.2 mm Hg; p ¼
prosthesis in borderline ranges with no improvement
0.023) (Figure 1).
after postdilation (1 patient).
DISCUSSION
in 34.4% of the patients. Other series report post-
In the present series, post-dilation was performed dilation rates of 1% to 4%. Unpublished results from We report our initial experience of in-hospital and
the PARTNER II S3 program (12) have reported a post-
30-day event rates according to VARC-2 in a medium-
dilation rate between 11% and 15%. The underlying
sized patient population using a novel balloon-
reasons for the observed elevated post-dilation rate
expandable THV. We found excellent outcomes
in our series compared with other groups remain
using the S3 THV with very low mortality and high
unclear; however, using this strategy we were able to
device success rates. With the final PARTNER II S3
achieve excellent procedural results and outcome at
results pending, our study may be of interest to cli-
30 days.
nicians using this novel device.
VASCULAR
COMPLICATIONS
AND
BLEEDING.
VARC-2–DEFINED EARLY SAFETY AT 30 DAYS AND
Vascular complications after TAVR are a frequent
DEVICE SUCCESS. The main finding of this single-
complication and the main determinant of bleeding
center observational study is the high rate of VARC-
and mortality (23,24). Previous devices, requiring
2–defined device success (97.6%) and freedom of the
larger sheaths (24- to 26-F inner diameter), showed an
composite VARC-2–defined early safety endpoint at
incidence of major vascular complications ranging
30 days of 90.0% with an all-cause mortality rate
from 5% to 23% (18). With increasing experience and
of <1%. The VARC-2–defined composite endpoint
evolution of TAVR systems, this figure has consider-
early safety at 30 days summarizes important
ably decreased to w16% (3). Major vascular compli-
measures of complications and mortality and has
cations and life-threatening bleeding with the novel
been proposed for assessment of patient safety in
low-profile S3 THV (14- to 16-F inner diameter)
TAVR. Two recent meta-analyses have reported
range between 0 and 5.9% and 0 and 5.4%, respec-
freedom from VARC-2–defined early safety com-
tively (8,10–12). In the present study, we observed
posite endpoint at 30 days in w77% of the cases
comparable rates with major vascular complications
(17,18). Compared with these data, in the present
in 3.6% and life-threatening bleeding in 4.8% of
intermediate-risk population, we observed freedom
patients.
of this composite endpoint in 90% after 30 days, indicating an excellent safety profile of this novel device. Device success is a composite endpoint especially driven by the presence of residual moderate or severe paravalvular leakage, showing an incidence of 12% to 24% in the literature (19). As emerging evidence indicates a strong influence of paravalvular leakage on long-term mortality (17,20), much effort has been undertaken to develop techniques to reduce its incidence in the development of new THVs. The S3 fea-
STROKE. New cerebrovascular events after TAVR are
frequent but are silent in most cases. The incidence of 30-day clinically apparent major or disabling stroke is in the range of w2% to 4% (25–28) and seems to be independent of valve type and access (27). We observed a rate of disabling stroke of 1.6%, comparing favorably with these previous data being at the lower limit of the expected. Other groups, treating patients with a transfemoral S3 THV, have reported similar stroke rates ranging from 0 to 2% (8,10–12).
tures a sealing skirt at its lower portion and a more
NEW PERMANENT PACEMAKER IMPLANTATIONS.
accurate positioning mechanism and thus may pro-
The incidence of new permanent pacemaker implan-
vide a better prevention of paravalvular leaks. With
tations after TAVR using balloon-expandable valves
moderate or severe paravalvular leakage of 2.0% in
ranges between 5% and 12% (1,29,30). Although the
this study, and 0 to 3.8% in other studies (8,10,11),
impact on clinical outcome remains controversial, no
hemodynamic results of the S3 THV seem superior
impact on survival has been observed (31,32). How-
compared with older THV and comparable to other
ever, new permanent pacemakers may limit clinical
newer
Direct
benefit due to the loss of atrioventricular synchrony
Flow Medical (21) or the Lotus THV (22). Although
and right ventricular pacing (33) and procedural costs
the occurrence of paravalvular leakage is probably
may increase (34).
generation
devices
such
as
the
multifactorial, in the case of moderate paravalvular
Preliminary studies have reported new permanent
leakage in our population, the most likely reasons
pacemakers after TAVR with the S3 THV in 13% to
were a slightly high position of the valve (n ¼ 3), heavy
25.5% (9–11). In the yet unpublished PARTNER II S3
calcification (n ¼ 1), and selection of the smaller
program, the new permanent pacemaker rate in the
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30-Day Outcome With New Balloon-Expandable Device
entire transfemoral intermediate-risk cohort was
The main finding of this single-center observational
10.4% (12). We observed a 30-day rate of new per-
study is the high device success rate of 97.6%,
manent pacemaker in 15.2% of the entire cohort and
freedom of VARC-2–defined early safety composite
in 16.8% of the patients without a previous pace-
endpoint in 90%, and a 30-day all-cause mortality
maker at 30 days. The development of novel devices
rate <1%. In addition to these promising clinical re-
should weigh potential improvements, such as mini-
sults, we observed an increased rate of new perma-
mizing paravalvular leakage and vascular complica-
nent pacemaker implantations.
tions,
against
an
increase
in
new
permanent
pacemaker implantations and new-onset conduction
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
abnormalities. Minimizing these complications is
Oliver
mandatory for further application of TAVR, especially
Deutsches Herzzentrum München, Klinik für Herz-
in intermediate-risk patients. The potential de-
und Kreislauferkrankungen, Technische Universität
terminants of new permanent pacemaker implanta-
München, Lazarettstr. 36, 80636 Munich, Germany.
tions and conduction abnormalities include the high
E-mail:
frame of the S3 THV and the deeper extension into
[email protected].
Husser
and
Dr.
Christian
[email protected]
Hengstenberg,
OR
christian.
the left ventricular outflow tract (7). Depth of implantation has already been shown to be associated
PERSPECTIVES
with pacemaker implantation after TAVR with the S3 THV (9). However, the learning curve may play a role,
WHAT IS KNOWN? To date, only data from small series and
and the appropriateness of manufacturer’s sizing
1 modest-sized multicenter study on the novel SAPIEN 3 trans-
recommendations may require critical appraisal.
catheter heart valve are available, and clinical efficacy and
Further research to identify the determinants of new
30-day outcome are still unclear.
conduction abnormalities is warranted to potentially reduce permanent pacemaker implantations using
WHAT IS NEW? In this medium-size single-center observa-
this novel device.
tional study, we found excellent 30-day outcomes with very low
STUDY
LIMITATIONS. This
was an observational
study from a single center without center-independent adjudication of post-procedural results and the lack of independent core lab assessment of paravalvular leakage on echocardiography.
rates of clinical adverse events according to the VARC-2 composite early safety endpoint with the SAPIEN 3. In a real-world experience outside of trial constraints, high rates of device success could be achieved. However, the need for new pacemaker implantation appears to be slightly increased. WHAT IS NEXT? Confirmation of these excellent short-term
CONCLUSIONS
outcomes and maintenance in the long term are warranted.
We report our first experience using a novel balloonexpandable THV redesigned to minimize residual
The underlying mechanisms of new permanent pacemaker implantations merit further research.
paravalvular leakage and with low-profile sheaths.
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5. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aortic-valve implantation in high-
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6. Ludman PF, Moat N, de Belder MA, et al. Transcatheter aortic valve implantation in the United Kingdom: temporal trends, predictors of outcome, and 6-year follow-up: a report from the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012. Circulation 2015;131: 1181–90. 7. Binder RK, Rodés-Cabau J, Wood DA, et al. Transcatheter aortic valve replacement with the SAPIEN 3: a new balloon-expandable transcatheter heart valve. J Am Coll Cardiol Intv 2013; 6:293–300. 8. Amat-Santos IJ, Dahou A, Webb J, et al. Comparison of hemodynamic performance of the
9. Tarantini G, Mojoli M, Purita P, et al. Unravelling the (arte)fact of increased pacemaker rate with the Edwards SAPIEN 3 valve. EuroIntervention 2015; 11:343–50. 10. Murray MI, Geis N, Pleger ST, et al. First experience with the new generation edwards sapien 3 aortic bioprosthesis: procedural results and short term outcome. J Interv Cardiol 2015;28: 109–16. 11. Webb J, Gerosa G, Lefèvre T, et al. Multicenter evaluation of a next-generation balloonexpandable transcatheter aortic valve. J Am Coll Cardiol 2014;64:2235–43.
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30-Day Outcome With New Balloon-Expandable Device
12. Kodali S, the Partner Trial Investigators. Clinical and echocardiographic outcomes at 30 days with the SAPIEN 3 TAVR system in inoperable, high-risk and intermediate-risk AS patients. Presented at: ACC 2015, March 14–16, 2015; San Diego, CA. 13. Kappetein AP, Head SJ, Généreux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Am Coll Cardiol 2012;60:1438–54. 14. Achenbach S, Delgado V, Hausleiter J, Schoenhagen P, Min JK, Leipsic JA. SCCT expert consensus document on computed tomography imaging before transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR). J Cardiovasc Comput Tomogr 2012; 6:366–80.
comprehensive review of the literature. J Am Coll Cardiol 2013;61:1125–36.
meta-analysis and systematic review of literature. J Am Coll Cardiol 2014;63:2101–10.
20. Kodali S, Pibarot P, Douglas PS, et al. Paravalvular regurgitation after transcatheter aortic valve replacement with the Edwards sapien valve in the PARTNER trial: characterizing patients and impact on outcomes. Eur Heart J 2015;36:44956.
28. Nombela-Franco L, Webb JG, de Jaegere PP, et al. Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve
21. Schofer J, Colombo A, Klugmann S, et al. Prospective multicenter evaluation of the Direct Flow Medical transcatheter aortic valve. J Am Coll Cardiol 2013;63:763–8.
29. Eltchaninoff H, Prat A, Gilard M, et al. Transcatheter aortic valve implantation: early results of the FRANCE (FRench Aortic National CoreValve and Edwards) registry. Eur Heart J 2011;32:191–7.
22. Meredith Am IT, Walters DL, Dumonteil N, et al. Transcatheter aortic valve replacement for severe symptomatic aortic stenosis using a repositionable valve system: 30-day primary endpoint results from the REPRISE II study. J Am Coll Car-
30. Siontis GC, Jüni P, Pilgrim T, et al. Predictors of permanent pacemaker implantation in patients with severe aortic stenosis undergoing TAVR: a meta-analysis. J Am Coll Cardiol 2014;64:129–40.
implantation. Circulation 2012;126:3041–53.
diol 2014;64:1339–48.
31. Buellesfeld L, Stortecky S, Heg D, et al. Impact of permanent pacemaker implantation on clinical
15. Holzamer A, Sitka E, Hengstenberg C, et al. Multislice computed tomography-based prediction of the implantation plane in transcatheter aortic valve implantation: determination of the line of perpendicularity and the implanter’s views. Eur J Cardiothorac Surg 2015;48:879–86.
23. Steinvil A, Leshem-Rubinow E, Halkin A, et al. Vascular complications after transcatheter aortic valve implantation and their association with
outcome among patients undergoing transcatheter aortic valve implantation. J Am Coll Cardiol 2012;60:493–501.
16. Kasel AM, Cassese S, Leber AW, von Scheidt W, Kastrati A. Fluoroscopy-guided aortic root imaging for TAVR follow the right cusp rule. J Am Coll Cardiol Img 2013;6:274–5.
24. Généreux P, Webb JG, Svensson LG, et al. Vascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. J Am Coll Cardiol 2012;60:1043–52.
17. Chieffo A, Buchanan GL, Van Mieghem NM, et al. Transcatheter aortic valve implantation with the Edwards SAPIEN versus the Medtronic CoreValve Revalving system devices: a multicenter collaborative study: the PRAGMATIC Plus Initiative (Pooled-RotterdAm-Milano-Toulouse In Collaboration). J Am Coll Cardiol 2013;61: 830–6. 18. Généreux P, Head SJ, Van Mieghem NM, et al. Clinical outcomes after transcatheter aortic valve replacement using valve academic research consortium definitions: a weighted meta-analysis of 3,519 patients from 16 studies. J Am Coll Cardiol 2012;59:2317–26. 19. Généreux P, Head SJ, Hahn R, et al. Paravalvular leak after transcatheter aortic valve replacement: the new Achilles’ heel? A
mortality reevaluated by the Valve Academic Research Consortium definitions. Am J Cardiol 2015;115:100–6.
25. Eggebrecht H, Schmermund A, Voigtländer T, Kahlert P, Erbel R, Mehta RH. Risk of stroke after transcatheter aortic valve implantation (TAVI): a meta-analysis of 10,037 published patients. EuroIntervention 2012;8:129–38. 26. Fearon WF, Kodali S, Doshi D, et al. Outcomes after transfemoral transcatheter aortic valve replacement: a comparison of the randomized PARTNER (Placement of AoRTic TraNscathetER Valves) trial with the NRCA (Nonrandomized
32. Urena M, Webb JG, Tamburino C, et al. Permanent pacemaker implantation following transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function. Circulation 2013;129:1233–43. 33. Tops LF, Schalij MJ, Bax JJ. The effects of right ventricular apical pacing on ventricular function and dyssynchrony implications for therapy. J Am Coll Cardiol 2009;54:764–76. 34. Chevreul K, Brunn M, Cadier B, et al. Cost of transcatheter aortic valve implantation and factors associated with higher hospital stay cost in patients of the FRANCE (FRench Aortic National CoreValve and Edwards) registry. Arch Cardiovasc Dis 2013;106:209–19.
27. Athappan G, Gajulapalli RD, Sengodan P, et al.
KEY WORDS aortic valve stenosis, outcome, SAPIEN 3, transfemoral transcatheter aortic valve implantation, VARC-2
Influence of transcatheter aortic valve replacement strategy and valve design on stroke after transcatheter aortic valve replacement: a
A PPE NDI X For a supplemental table, please see the online version of this article.
Continued Access) registry. J Am Coll Cardiol Intv 2014;7:1245–51.
VOL. 8, NO. 14, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2015.08.014
Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Balloon-Expandable Transcatheter Heart Valve A Single-Center Experience Oliver Husser, MD,* Costanza Pellegrini, MD,* Thorsten Kessler, MD,* Christof Burgdorf, MD,* Hannah Thaller,* N. Patrick Mayr, MD,y Ilka Ott, MD,* Albert M. Kasel, MD,* Heribert Schunkert, MD,*z Adnan Kastrati, MD,*z Christian Hengstenberg, MD*z
ABSTRACT OBJECTIVES Evaluation of 30-day outcomes after transcatheter aortic valve replacement (TAVR) with the novel balloon-expandable SAPIEN 3 (S3) transcatheter heart valve (THV) (Edwards Lifesciences, Irvine, California) emphasizing the updated Valve Academic Research Consortium (VARC-2) criteria. BACKGROUND Preliminary data on clinical performance with the S3 THV are promising. However, information regarding 30-day outcome is limited. METHODS A total of 250 consecutive patients undergoing transfemoral TAVR with the S3 THV at our center were enrolled, and outcomes according to VARC-2 criteria were analyzed at 30 days. RESULTS The mean age was 81.0 6.2 years, median logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) and Society of Thoracic Surgeons score were 12.1% and 4.4%, respectively. VARC-2–defined device success was achieved in 244 patients (97.6%); moderate paravalvular leakage developed in 5 patients (2.0%). One patient (0.4%) died of a noncardiac cause and 8 patients (3.2%) had a stroke. Life-threatening bleeding and major vascular complications occurred in 12 (4.8%) and 9 (3.6%) of the patients, respectively. From discharge to 30 days, 5 patients (2.0%) were hospitalized due to valve-related symptoms or worsening of heart failure. The VARC-2 composite early safety endpoint was observed in 25 patients (10.0%). Permanent pacemaker implantation rate at 30 days was 15.2%. Myocardial infarction, coronary obstruction requiring intervention, valve-related dysfunction, and endocarditis were not observed. CONCLUSIONS We found very good 30-day results using the novel S3 THV with a low rate of clinical events according to VARC-2 criteria. The S3 THV is associated with high procedural success and favorable early safety profile. The need for pacemaker implantations appears to be more frequent than with its predecessor. (J Am Coll Cardiol Intv 2015;8:1809–16) © 2015 by the American College of Cardiology Foundation.
From the *Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany; yDeutsches Herzzentrum München, Institut für Anästhesiologie, Technische Universität München, Munich, Germany; zDeutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK) e.V. (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. Dr. Husser received minor travel fees from Edwards Lifesciences. Dr. Kasel is a consultant and proctor for Edwards Lifesciences. Dr. Hengstenberg is a proctor for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 5, 2015; revised manuscript received August 7, 2015, accepted August 13, 2015.
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30-Day Outcome With New Balloon-Expandable Device
T
ranscatheter aortic valve replace-
analysis. Therefore, the final study population con-
ment (TAVR) has rapidly evolved
sisted of 250 patients. All cases were discussed by the
from a novel technology to the
multidisciplinary heart team, and consensus was
preferred treatment for patients with severe
achieved regarding the therapeutic strategy. TAVR
symptomatic aortic stenosis who cannot un-
was performed in a hybrid operating suite with pa-
Association
dergo conventional surgical aortic valve
tients under general anesthesia or conscious seda-
TAVR = transcatheter aortic
replacement (1) and has been shown to be
tion. All patients provided written informed consent
valve replacement
noninferior in high-risk patients (2). Large
for the procedure.
THV = transcatheter heart
clinical registries have consistently reported
valve
excellent
S3 = SAPIEN 3
complication rates (6).
ABBREVIATIONS AND ACRONYMS MSCT = Multislice computed tomography
NYHA = New York Heart
outcomes
VARC-2 = Valve Academic
(3–5)
and
decreased
discharge, and at the 30-day follow-up visit. Left
Although, in part, this decrease may be attributable to increasing operator experience, the evolution of TAVR with novel transcatheter heart valves (THVs) and further iterations of delivery systems to reduce periprocedural complications also play an important part. Periprocedural complications include paravalvular leakage, new permanent pacemaker implantations, thromboembolic events, bleeding, and vascular complications. The SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California)
is
a
novel
TOMOGRAPHY DATA ANALYSIS. Transthoracic echo-
cardiography was performed before TAVR, before
SEE PAGE 1817
Research Consortium
ECHOCARDIOGRAPHY AND MULTISLICE COMPUTED
balloon-expandable
THV
featuring a lower profile delivery system (Commander, Edwards Lifesciences) to reduce the risk of vascular injury as well as access site complications and allows for rapid and accurate positioning. Additionally, this device features a sealing cuff to reduce paravalvular regurgitation (7). The S3 THV received the CE mark in Germany in January 2014. To date, only small series (8–10) and 1 modest-sized multicenter trial (11) have assessed this novel device and clinical efficacy, and 30-day outcome is still unclear. The upcoming final results of the large-scale multi-
ventricular ejection fraction, mean transvalvular gradient, and paravalvular regurgitation were determined. Discharge echocardiographic data were available for 242 patients, and 30-day echocardiographic follow-up was available in 185 patients. Multislice computed tomography (MSCT) was performed as part of the standard pre-procedural screening protocol. Aortic annulus measurements were assessed in multiple plane reconstructions according to the guidelines of the Society of Cardiovascular Computed Tomography (14). In short, the area and perimeter of the virtual aortic annulus were obtained by direct planimetry. The minimal and maximal diameter were determined, and the effective diameter was calculated as the sum of the minimal and maximal diameter divided by 2. Calcification of the valvular apparatus was assessed at the height of the aortic cusps, annulus, and the left ventricular outflow tract and visually graded as none, mild, moderate, and severe. Dedicated U.S. Food and Drug Administration–approved software (OsiriX MD 3.9.4, Pixmeo, Switzerland) was used.
center PARTNER II Trial: Placement of Aortic Trans-
PROSTHESIS SIZE SELECTION AND PROCEDURE.
catheter Valves (12) are still eagerly awaited.
The technical features of the S3 THV have been
Here we report our single-center experience using
described elsewhere (7,11). The device is available in
the S3 THV, according to the updated standardized
23-, 26-, and 29-mm sizes. The dimensions of a
endpoint definitions issued by the Valve Academic
nominally expanded S3 THV and the manufacturer’s
Research Consortium (VARC-2) (13) with special
sizing recommendations are given in Online Table 1.
emphasis on the composite early safety endpoint at
The final decision on prosthesis size was left to the
30 days.
discretion of the physicians performing the procedure based on MSCT measurements and taking into ac-
METHODS
count other anatomic features such as the presence and distribution of calcification, eccentricity of the
PATIENT POPULATION. Between January 2014 and
aortic annulus, and also the patient anatomy in case
March 2015, 261 consecutive patients with severe
of borderline sizing ranges.
symptomatic aortic stenosis were treated with trans-
The percentage of oversizing according to area was
femoral TAVR using the S3 THV at the Department
calculated using the formula: (nominal prosthesis
of Cardiology, Deutsches Herzzentrum München,
dimension/patient anatomy 1) 100. The adher-
Munich,
ence to the manufacturer’s sizing guidelines by area
Germany.
Patients
treated
with
other
devices or requiring valve-in-valve procedures due to
was categorized as “undersized,” “within range,” and
degenerated bioprostheses were excluded from the
“oversized.” The implantation plane was identified
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30-Day Outcome With New Balloon-Expandable Device
using previously described techniques, by either
was used to compare the proportions of patients in
calculation from the MSCT (15) or the combination of
New York Heart Association (NYHA) functional class
angiographic and fluoroscopic guidance (16). A pigtail
III/IV at baseline and 30 days. A 2-sided p value <0.05
was placed in the right coronary cusp, and an
was considered statistically significant for all anal-
orthogonal view of the 3 aortic cusps was confirmed
yses. IBM SPSS Statistics version 22 (IBM, Armonk,
by aortic angiography. Initially, the center dot was
New York) was used for all analyses.
placed at the middle of the virtual annulus, and the valve was expanded under rapid pacing. With
RESULTS
growing experience, to avoid excessively deep implantation of the prosthesis within the left ventricular
PATIENT CHARACTERISTICS. In total, 250 patients
outflow tract, this strategy was changed to a higher
undergoing transfemoral TAVR with the S3 THV were
position of the center dot in relation to the virtual
analyzed. Their mean age was 81.0 6.2 years, and
annulus plane.
43.6% were female. Baseline characteristics of the paravalvular
entire patient population are listed in Table 1. The risk
leakage was evident on post-deployment angiog-
profile included an elevated burden of comorbidities
raphy and/or transesophageal echocardiography or if
resulting in an intermediate-risk population (median
fluoroscopy
underexpansion
logistic EuroSCORE [European System for Cardiac
using the delivery system’s balloon and adding w1 to
Operative Risk Evaluation] I: 12.1%, EuroSCORE II:
2 ml to the recommended filling volume at the
4.2%, and Society of Thoracic Surgeons score: 4.4%).
operator’s discretion.
Left
Post-dilation
DEFINITION
was
revealed
OF
performed
prosthesis
ENDPOINTS
if
AND
ventricular
ejection
fraction
was
severely
FOLLOW-UP.
All data up to 30 days were prospectively collected during routine ambulatory visits at the outpatient clinic, by referring to the treating physician, and other hospital documentation or the patient directly. All clinical endpoints, procedural success, and the
T A B L E 1 Baseline Characteristics: Total Patients (N ¼ 250)
Clinical characteristics Age, yrs
81.0 6.2
Female
109 (43.6)
BMI, kg/m2
26.9 4.8
composite early safety endpoint at 30 days were
Logistic EuroSCORE I, %
categorized using VARC-2 criteria (13). In brief, device
EuroSCORE II, %
4.2 (2.6-7.4)
success was defined as the absence of procedural
STS score, %
4.4 (2.7-7.0)
mortality, correct positioning of a single prosthetic
NYHA functional class III/IV
heart valve in the proper anatomic location, and
COPD
31 (12.4)
Diabetes mellitus
72 (28.8)
intended performance. The occurrence of all-cause mortality, stroke, rehospitalization for worsening heart failure, vascular complications, bleeding, acute
GFR ml/min
12.1 (7.6-20.0)
167 (66.8)
52.4 22.1
Extracardiac arteriopathy
70 (28.0)
Peripheral vascular disease
36 (14.4)
kidney injury, myocardial infarction, valve-related
Previous stroke, major/minor
23 (9.2)
dysfunction, and endocarditis or valve thrombosis
Previous pacemaker
24 (9.6)
up to 30 days was assessed. The incidence of per-
Coronary artery disease
manent pacemaker implantation was recorded. The
Previous myocardial infarction
composite endpoint early safety at 30 days (all-cause
Previous PCI
mortality, stroke [disabling and nondisabling], lifethreatening bleeding, acute kidney injury (RIFLE [Risk, Injury, Failure, Loss, and End-stage kidney disease] 2 or 3 or renal replacement therapy), coronary artery obstruction requiring intervention, major
Previous CABG
170 (68.0) 23 (9.2) 102 (40.8) 15 (6.0)
Echocardiographic characteristics LVEF <35%
31 (12.4)
AR IIIþ
3 (1.2)
MR IIIþ
8 (3.2)
Electrocardiographic characteristics
vascular complication, and valve-related dysfunction
Atrial fibrillation
requiring repeat procedure) was evaluated.
RBBB
19 (7.6)
LBBB
7 (2.8)
75 (30.0)
STATISTICAL ANALYSIS. Continuous variables are
expressed as mean with the SD or the median with the interquartile range. A repeated-measures analysis of variance with the post hoc Bonferroni correction was used for within-patient repeated measures of mean transaortic gradient at baseline, after TAVR and at 30 days. McNemar test for correlated categorical data
Values are mean SD, n (%), or median (interquartile range). AR ¼ aortic regurgitation; BMI ¼ body mass index; CABG ¼ coronary artery bypass graft; COPD ¼ chronic obstructive pulmonary disease; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation GFR ¼ glomerular filtration rate; LBBB ¼ left bundle branch block; LVEF ¼ left ventricular ejection fraction; MR ¼ mitral regurgitation; NYHA ¼ New York Heart Association; PCI ¼ percutaneous coronary intervention; RBBB ¼ right bundle branch block; STS ¼ Society of Thoracic Surgeons.
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30-Day Outcome With New Balloon-Expandable Device
depressed (<35%) in 12.4% (31 of 250) of the patients. A previous pacemaker was present in 9.6% (24 of 250) of the patients. The median stay in the intensive care unit and the stay in hospital were 1.0 (1.0 to 2.0) and 5.0 (5.0 to 7.0) days, respectively. PROCEDURAL CHARACTERISTICS AND PROSTHESIS
T A B L E 3 MSCT-Derived Aortic Annular Anatomy and Degree of
Oversizing (N ¼ 248*)
Minimal diameter, mm
21.1 2.4
Maximal diameter, mm
27.1 2.7
Effective diameter, mm
24.1 2.4
Perimeter, mm
77.4 7.5
Area, cm2
SIZING. All patients underwent TAVR using the
Prosthesis oversizing by area, %
transfemoral access. Conscious sedation was used in
Eccentricity index
43.6% (109 of 250) of the patients. The 23-, 26-, and
Degree of calcification
4.7 0.9 7.2 (0.4 to 13.9) 0.2 0.1 (0–3)
29-mm S3 THVs were used in 42.8%, 37.2%, and
Cusps, moderate/severe
176 (70.4)
20.0% of the patients, respectively. Procedural char-
Annulus, moderate/severe
25 (10.0)
acteristics are shown in Table 2. MSCT measurements
LVOT, moderate/severe
of the aortic annulus are presented in Table 3. Measurements were evaluated for 248 patients because 1 patient did not undergo MSCT due to renal failure
17 (6.8)
Values are mean SD, median (interquartile range), or n (%). *Excluding patients without MSCT. LVOT ¼ left ventricular outflow tract; MSCT ¼ multislice computed tomography.
and 1 patient had not previously undergone MSCT. The mean aortic annular area was 4.7 0.9 cm 2,
56.4%, and it was mild in 41.6% and moderate in 2.0%
resulting in a median prosthesis oversizing by area of
of patients. No patient had severe paravalvular
7.2% (interquartile range: 0.4% to 13.9%). Prosthesis
leakage. Intended prosthesis performance was not
sizing was within the manufacturer’s recommended
achieved in 5 patients (2.0%) due to residual para-
range in 77.4%, undersized in 12.1%, and oversized in
valvular leakage more than grade II, and 1 patient
10.5% of the patients. Post-dilation was performed in
required a second valve due to severe paravalvular
34.4% (86 of 250).
leakage after the first valve implantation.
VARC-2–DEFINED DEVICE SUCCESS AND IN-HOSPITAL OUTCOME. VARC-2–defined
device
success
was
achieved in 97.6% (244 of 250) of the patients (Table 4). No intraprocedural death occurred. There was no post-implantation paravalvular leakage in
In-hospital outcome and complications are given in Table 5. No in-hospital death occurred. The stroke rate was 2.8% (7 of 250), with disabling strokes in 3 patients. Life-threatening bleeding and major vascular complications occurred in 4.4% (11 of 250) and 3.6% (9 of 250) of the patients, respectively. A new permanent pacemaker implantation was required in 35 patients (14.0%). Excluding patients with
T A B L E 2 Procedural Characteristics: Total Patients (N ¼ 250)
a permanent pacemaker at baseline, the incidence of
Prosthesis size, mm
new pacemaker implantation was 15.5% (25 of 226).
23
107 (42.8)
No myocardial infarction occurred. Acute kidney
26
93 (37.2)
injury (defined as RIFLE 2/3) occurred in 2.0%
29
50 (20.0)
(5 of 250). Postprocedural echocardiography showed a
Conscious sedation
109 (43.6)
ECMO Prophylactic Emergency Pre-dilation Standard balloon*
2 (0.8)
(43.3 15.2 mm Hg to 12.1 5.1 mm Hg; p < 0.0001)
1 (0.4)
(Figure 1).
246 (98.4) 175 (70.0)
Other balloon
71 (28.4)
Post-dilation†
86 (34.4)
Procedural time, min
59.9 22.9
Fluoroscopy time, min
13.4 5.7
Contrast, ml
113.9 62.6
Days in hospital
5.0 (5.0–7.0)
Days in the intensive care unit
1.0 (1.0–2.0)
Values are n (%), mean SD, or median (interquartile range). *Balloon with the recommended volume included with the delivery system and transcatheter heart valve (THV) (i.e., 20-mm balloon for 23-mm THV, 23-mm for 26-mm THV, and 25-mm for 29 mm-THV). †Post-dilation was performed using the delivery system’s balloon and adding w1 to 2 ml to the recommended filling volume at the operator’s discretion. ECMO ¼ extracorporeal membrane oxygenation.
significant decrease in mean transvalvular gradient
T A B L E 4 VARC-2–Defined Device Success (N ¼ 250)
Device success Procedural mortality Intended performance* Multiple valves
244 (97.6) 0 (0) 245 (98.0) 1 (0.4)
Correct position of the device in the proper anatomical location
250 (100)
Successful vascular access, delivery, and deployment of the device and successful retrieval of the delivery system
249 (99.6)
Values are n (%). *No prosthesis mismatch, mean aortic valve gradient <20 mm Hg or peak velocity <3 m/s, without moderate or severe prosthetic valve aortic regurgitation.
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30-Day Outcome With New Balloon-Expandable Device
T A B L E 5 Clinical Outcome In-Hospital and at 30 Days
In-Hospital Events (N ¼ 250)
F I G U R E 1 Mean Transvalvular Gradient at Baseline, Discharge, and 30 Days
At 30 Days* (N ¼ 250)
Mortality All-cause mortality
0 (0)
Noncardiac mortality
0 (0)
1 (0.4) 1 (0.4)
Cardiac mortality
0 (0)
0 (0)
All stroke
7 (2.8)
8 (3.2)
Disabling stroke
3 (1.2)
4 (1.6)
Nondisabling stroke
4 (1.6)
4 (1.6)
TIA
1 (0.4)
1 (0.4)
—
5 (2.0)
Neurological complications
Hospitalization for valve-related symptoms or worsened CHF Major vascular complication
9 (3.6)
9 (3.6)
Life-threatening bleeding
11 (4.4)
12 (4.8)
AKI 2/3, including renal replacement therapy
5 (2.0)
5 (2.0)
Coronary artery obstruction requiring intervention
0 (0)
0 (0)
Myocardial infarction
0 (0)
0 (0)
Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR)
0 (0)
0 (0)
Endocarditis
0 (0)
0 (0)
Valve thrombosis
0 (0)
NYHA functional class III/IV New pacemaker† VARC-2 early safety composite endpoint at 30 days
Mean transvalvular gradient at baseline, discharge, and 30 days in 185 patients with complete echocardiographic data showing a significant improvement in the mean transvalvular gradient after transcatheter aortic valve replacement and at 30 days.
0 (0)
—
17 (6.8)
proportion of patients in NYHA functional class III/IV
35 (14.0)
38 (15.2)
—
before and after TAVR (66.8% [167 of 250] vs. 6.8% [17
25 (10.0)
of 250]; p < 0.001). Of the patients who were hospitalized for worsening heart failure within 30 days
Values are n (%). *Events after hospital discharge until 30 days not available for 1 patient who was lost to follow-up due to inability to contact. †Percentage given for the entire cohort as the denominator; new pacemaker rate in hospital and at 30 days in patients without a previous pacemaker was 15.5% (35 of 226) and 16.8% (38 of 226), respectively.
(2.0%, 5 of 250), all showed NYHA functional class
AKI ¼ acute kidney injury; BAV ¼ balloon aortic valvuloplasty; CHF ¼ congestive heart failure; NYHA ¼ New York Heart Association; SAVR ¼ surgical aortic valve replacement; TAVR ¼ transcatheter aortic valve replacement; TIA ¼ transient ischemic attack; VARC ¼ Valve Academic Research Consortium.
gradient was stable from discharge examination to
lower than III at the 30-day visit. Echocardiographic data at 30 days were available for 185 patients. Mean
F I G U R E 2 NYHA Functional Class at Baseline and at 30 Ddays
VARC-2–DEFINED EARLY SAFETY AT 30 DAYS.
Follow-up at 30 days was complete in 249 patients. One patient was lost to follow-up due to inability to contact. The 30-day event-free rate was 90.0% (225 of 250), with the composite early safety endpoint observed in 10.0% (25 of 250) (Table 5). From hospital discharge to 30 days, 1 case of disabling stroke, 1 case of life-threatening bleeding, and 3 permanent pacemaker implantations were observed, resulting in a 30-day event rate of 3.2% (8 of 250), 4.8% (12 of 250), and 15.2% (38 of 250), respectively. No major vascular complication, myocardial infarction, endocarditis, or valve thrombosis was recorded from discharge to 30 days. One patient (0.4%) died of sepsis with multiorgan failure. Patients’ symptoms markedly ameliorated with an improvement in NYHA functional class in 89.2%
New York Heart Association (NYHA) functional class at baseline and discharge for
of the patients (Figure 2). Using the McNemar test,
250 patients with complete follow-up at 30 days.
there was a statistically significant difference in the
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30-Day Outcome With New Balloon-Expandable Device
30 days (12.1 5.1 mm Hg to 11.2 4.2 mm Hg; p ¼
prosthesis in borderline ranges with no improvement
0.023) (Figure 1).
after postdilation (1 patient).
DISCUSSION
in 34.4% of the patients. Other series report post-
In the present series, post-dilation was performed dilation rates of 1% to 4%. Unpublished results from We report our initial experience of in-hospital and
the PARTNER II S3 program (12) have reported a post-
30-day event rates according to VARC-2 in a medium-
dilation rate between 11% and 15%. The underlying
sized patient population using a novel balloon-
reasons for the observed elevated post-dilation rate
expandable THV. We found excellent outcomes
in our series compared with other groups remain
using the S3 THV with very low mortality and high
unclear; however, using this strategy we were able to
device success rates. With the final PARTNER II S3
achieve excellent procedural results and outcome at
results pending, our study may be of interest to cli-
30 days.
nicians using this novel device.
VASCULAR
COMPLICATIONS
AND
BLEEDING.
VARC-2–DEFINED EARLY SAFETY AT 30 DAYS AND
Vascular complications after TAVR are a frequent
DEVICE SUCCESS. The main finding of this single-
complication and the main determinant of bleeding
center observational study is the high rate of VARC-
and mortality (23,24). Previous devices, requiring
2–defined device success (97.6%) and freedom of the
larger sheaths (24- to 26-F inner diameter), showed an
composite VARC-2–defined early safety endpoint at
incidence of major vascular complications ranging
30 days of 90.0% with an all-cause mortality rate
from 5% to 23% (18). With increasing experience and
of <1%. The VARC-2–defined composite endpoint
evolution of TAVR systems, this figure has consider-
early safety at 30 days summarizes important
ably decreased to w16% (3). Major vascular compli-
measures of complications and mortality and has
cations and life-threatening bleeding with the novel
been proposed for assessment of patient safety in
low-profile S3 THV (14- to 16-F inner diameter)
TAVR. Two recent meta-analyses have reported
range between 0 and 5.9% and 0 and 5.4%, respec-
freedom from VARC-2–defined early safety com-
tively (8,10–12). In the present study, we observed
posite endpoint at 30 days in w77% of the cases
comparable rates with major vascular complications
(17,18). Compared with these data, in the present
in 3.6% and life-threatening bleeding in 4.8% of
intermediate-risk population, we observed freedom
patients.
of this composite endpoint in 90% after 30 days, indicating an excellent safety profile of this novel device. Device success is a composite endpoint especially driven by the presence of residual moderate or severe paravalvular leakage, showing an incidence of 12% to 24% in the literature (19). As emerging evidence indicates a strong influence of paravalvular leakage on long-term mortality (17,20), much effort has been undertaken to develop techniques to reduce its incidence in the development of new THVs. The S3 fea-
STROKE. New cerebrovascular events after TAVR are
frequent but are silent in most cases. The incidence of 30-day clinically apparent major or disabling stroke is in the range of w2% to 4% (25–28) and seems to be independent of valve type and access (27). We observed a rate of disabling stroke of 1.6%, comparing favorably with these previous data being at the lower limit of the expected. Other groups, treating patients with a transfemoral S3 THV, have reported similar stroke rates ranging from 0 to 2% (8,10–12).
tures a sealing skirt at its lower portion and a more
NEW PERMANENT PACEMAKER IMPLANTATIONS.
accurate positioning mechanism and thus may pro-
The incidence of new permanent pacemaker implan-
vide a better prevention of paravalvular leaks. With
tations after TAVR using balloon-expandable valves
moderate or severe paravalvular leakage of 2.0% in
ranges between 5% and 12% (1,29,30). Although the
this study, and 0 to 3.8% in other studies (8,10,11),
impact on clinical outcome remains controversial, no
hemodynamic results of the S3 THV seem superior
impact on survival has been observed (31,32). How-
compared with older THV and comparable to other
ever, new permanent pacemakers may limit clinical
newer
Direct
benefit due to the loss of atrioventricular synchrony
Flow Medical (21) or the Lotus THV (22). Although
and right ventricular pacing (33) and procedural costs
the occurrence of paravalvular leakage is probably
may increase (34).
generation
devices
such
as
the
multifactorial, in the case of moderate paravalvular
Preliminary studies have reported new permanent
leakage in our population, the most likely reasons
pacemakers after TAVR with the S3 THV in 13% to
were a slightly high position of the valve (n ¼ 3), heavy
25.5% (9–11). In the yet unpublished PARTNER II S3
calcification (n ¼ 1), and selection of the smaller
program, the new permanent pacemaker rate in the
Husser et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 8, NO. 14, 2015 DECEMBER 21, 2015:1809–16
30-Day Outcome With New Balloon-Expandable Device
entire transfemoral intermediate-risk cohort was
The main finding of this single-center observational
10.4% (12). We observed a 30-day rate of new per-
study is the high device success rate of 97.6%,
manent pacemaker in 15.2% of the entire cohort and
freedom of VARC-2–defined early safety composite
in 16.8% of the patients without a previous pace-
endpoint in 90%, and a 30-day all-cause mortality
maker at 30 days. The development of novel devices
rate <1%. In addition to these promising clinical re-
should weigh potential improvements, such as mini-
sults, we observed an increased rate of new perma-
mizing paravalvular leakage and vascular complica-
nent pacemaker implantations.
tions,
against
an
increase
in
new
permanent
pacemaker implantations and new-onset conduction
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
abnormalities. Minimizing these complications is
Oliver
mandatory for further application of TAVR, especially
Deutsches Herzzentrum München, Klinik für Herz-
in intermediate-risk patients. The potential de-
und Kreislauferkrankungen, Technische Universität
terminants of new permanent pacemaker implanta-
München, Lazarettstr. 36, 80636 Munich, Germany.
tions and conduction abnormalities include the high
E-mail:
frame of the S3 THV and the deeper extension into
[email protected].
Husser
and
Dr.
Christian
[email protected]
Hengstenberg,
OR
christian.
the left ventricular outflow tract (7). Depth of implantation has already been shown to be associated
PERSPECTIVES
with pacemaker implantation after TAVR with the S3 THV (9). However, the learning curve may play a role,
WHAT IS KNOWN? To date, only data from small series and
and the appropriateness of manufacturer’s sizing
1 modest-sized multicenter study on the novel SAPIEN 3 trans-
recommendations may require critical appraisal.
catheter heart valve are available, and clinical efficacy and
Further research to identify the determinants of new
30-day outcome are still unclear.
conduction abnormalities is warranted to potentially reduce permanent pacemaker implantations using
WHAT IS NEW? In this medium-size single-center observa-
this novel device.
tional study, we found excellent 30-day outcomes with very low
STUDY
LIMITATIONS. This
was an observational
study from a single center without center-independent adjudication of post-procedural results and the lack of independent core lab assessment of paravalvular leakage on echocardiography.
rates of clinical adverse events according to the VARC-2 composite early safety endpoint with the SAPIEN 3. In a real-world experience outside of trial constraints, high rates of device success could be achieved. However, the need for new pacemaker implantation appears to be slightly increased. WHAT IS NEXT? Confirmation of these excellent short-term
CONCLUSIONS
outcomes and maintenance in the long term are warranted.
We report our first experience using a novel balloonexpandable THV redesigned to minimize residual
The underlying mechanisms of new permanent pacemaker implantations merit further research.
paravalvular leakage and with low-profile sheaths.
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KEY WORDS aortic valve stenosis, outcome, SAPIEN 3, transfemoral transcatheter aortic valve implantation, VARC-2
Influence of transcatheter aortic valve replacement strategy and valve design on stroke after transcatheter aortic valve replacement: a
A PPE NDI X For a supplemental table, please see the online version of this article.
Continued Access) registry. J Am Coll Cardiol Intv 2014;7:1245–51.