- Email: [email protected]
Techniques and Outcomes of Percutaneous Aortic Paravalvular Leak Closure
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 9, NO. 23, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-8798/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jcin.2016.08.038
STRUCTURAL
Techniques and Outcomes of Percutaneous Aortic Paravalvular Leak Closure Mohamad Alkhouli, MD, Mohammad Sarraf, MD, Elad Maor, MD, Saurabh Sanon, MBBS, Allison Cabalka, MD, Mackram F. Eleid, MD, Donald J. Hagler, MD, Peter Pollak, MD, Guy Reeder, MD, Charanjit S. Rihal, MD
ABSTRACT OBJECTIVES The aim of this study is to provide a summary of the currently applied aortic paravalvular leak (PVL) closure techniques and describe the procedural and long-term outcomes in a large consecutive cohort of patients. BACKGROUND Percutaneous repair has emerged as an effective therapy for patients with PVL. To date, clinical outcome data on percutaneous closure of aortic PVL are limited. METHODS All patients who underwent catheter-based treatment of aortic PVL between 2006 and 2015 were identified. Procedural and short-term results were assessed. Patients were contacted for clinical events and symptoms. RESULTS Eighty-six procedures were performed in 80 patients. The mean age was 68 15 years, and 70% were men. The primary indications for PVL closure were symptoms of heart failure, hemolysis, and both in 83%, 5%, and 12%, respectively. Successful device deployment was accomplished in 94 defects (90%). Reduction in PVL to mild or less was achieved in 62% of patients. In-hospital major adverse events occurred in 8% of procedures. Symptomatic improvement at 30 days was achieved in 64% of patients. Patients who had reduction in the PVL grade to mild or less experienced more improvement in New York Heart Association functional class (from 2.93 0.62 to 1.72 0.73) compared with those with mild or greater residual leak (from 3.03 0.57 to 2.52 0.74) (p < 0.001). In patients with severe hemolysis (n ¼ 8), transfusion requirements were eliminated in 7 (88%) after PVL closure. Kaplan-Meier survival analysis showed that the cumulative probability of freedom from repeat surgery at 2 years was 98 2% in patients who had mild or less residual leak compared with 68 10% in patients with higher grades of residual PVL (log-rank p ¼ 0.004). CONCLUSIONS Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to a grade of mild or less. Therefore, attempts should be made to reduce PVL as much as possible. (J Am Coll Cardiol Intv 2016;9:2416–26) © 2016 by the American College of Cardiology Foundation.
P
aravalvular leak (PVL) occurs in 5% to 17% of patients
after
valve
replacement
Percutaneous repair has emerged as an effective ther-
surgery
apy for patients with PVL, with feasibility and efficacy
(1–4). For symptomatic patients, repeat sur-
demonstrated in multiple studies (8–12). Although the
gery has been the traditional treatment of choice,
principles of transcatheter closure of mitral and aortic
but it is associated with high operative mortality and
PVL are similar, the techniques and procedural
variable results even in the modern era (1,4–7).
complexity differ significantly (13). Mitral PVL closure
From the Divisions of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 21, 2016; revised manuscript received August 22, 2016, accepted August 25, 2016.
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
2417
Percutaneous Aortic Paravalvular Leak Closure
is more intricate than aortic PVL because of some
(Rochester, Minnesota) before January 10,
ABBREVIATIONS
procedural and leak-specific characteristics. To date,
2016. The indications for percutaneous repair
AND ACRONYMS
the largest series examining the outcomes of percuta-
were moderate or severe PVL with severe or
neous PVL closure included only a small number of
life-style-limiting dyspnea (New York Heart
patients with aortic PVL (10,12,13).
Association [NYHA] functional class III or IV
AVPII = Amplatzer Vascular Plug II
IE = infective endocarditis
We hypothesized that aortic PVL closure can be
or class II with significant life-style or occu-
achieved with high success and low complications
pational impairment) or clinically significant
rates and that the degree of PVL reduction correlates
hemolytic anemia. Patients who had active
with symptomatic improvement and clinical out-
endocarditis and those who had large leaks
comes. In this report, we review the commonly
involving more than one-half of the circum-
applied techniques in aortic PVL closure and provide
ference of the sewing ring, or rocking motion
comprehensive data on the procedural and long-term
of the valve, were referred for surgical repair. Clini-
NYHA = New York Heart Association
PVL = paravalvular leak TAVR = transcatheter aortic valve replacement
outcomes of a large consecutive cohort of patients
cally significant hemolytic anemia was defined as
referred for aortic PVL closure.
symptomatic anemia (hemoglobin <11 g/dl in women
SEE PAGE 2427
METHODS
and <12.5 g/dl in men), with laboratory evidence of intravascular hemolysis. GRADING OF AORTIC PVL. The assessment of the
severity of aortic PVL incorporated a multifaceted STUDY POPULATION. The Mayo Clinic Institutional
approach. This included echocardiographic, invasive
Review Board approved this investigation. We retro-
hemodynamic, and angiographic measures. Semi-
spectively identified patients who underwent percu-
quantitative echocardiographic parameters were used
taneous repair of aortic PVL at the Mayo Clinic
in all cases to grade the PVL as mild, mild to
F I G U R E 1 Utility of Echocardiography in Aortic Paravalvular Leak Closure
Transeophageal echocardiography (TEE) revealing significant para-aortic leak in 2 patients (Patient#1, A, B) and (Patient#2, C to F). (A) Moderate posterior para-aortic leak pre-closure (arrow). (B) Trivial residual leak after deployment with a 12-mm Amplatzer Vascular Plug II (AVPII) device (arrow). The star indicates the delivery cable before device release. (C) 3-dimensional TEE showing severe anteriomedial para-aortic leak pre-closure (arrow). (D) 3-dimensional TEE showing successful closure of the leak with 3 AVPII devices (arrow). (E) 3D-dimensional TEE in the same patient showing an interval development of a de novo leak at a different anterior location 9 months after the index procedure. (F) 3D-dimensional TEE showing successful closure of the leak with 1 AVPII device (dashed arrow). The plugs from the prior closure procedure are indicated by the arrow.
2418
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 2 Utility of Cardiac Computed Tomography in the Pre-Procedural Planning of Aortic Paravalvular Leak Closure
(A to C) Identification of the location and dimensions of an aortic paravalvular leak on cardiac computed tomography. The paravalvular leak can be readily located in a modified 4-chamber view (A), a modified 2-chamber view (B), and a modified short-axis views (C) (yellow arrows). The distance between the neck of the paravalvular leak and the ostium of the adjacent coronary artery is shown in D. The black star indicates the ostium of the left main coronary artery. AO ¼ aorta; LA ¼ left atrium; LV ¼ left ventricle.
moderate, moderate, or severe: 1) the PVL jet width
functional class by at least 1 class and/or elimination
(vena contracta) measured in the short- and long-axis
of need for transfusion in cases of severe hemolysis.
views at the level of the prosthesis sewing ring and in
Patients were contacted by telephone survey to
the left ventricular outflow tract; 2) assessment of
determine occurrence of adverse events, symptoms,
diastolic flow reversal in the descending thoracic and
and clinical status. In addition, the dates of death of
abdominal aorta; and 3) measurement of deceleration
deceased patients were verified by querying the
rate by pressure half-time (14). In the presence of
National Death Index, a centralized database of death
multiple defects, the sum of regurgitation from these
record information on file in state vital statistics
defects was used. Quantitative Doppler parameters
offices (16).
(e.g., regurgitant volume) were also used to confirm the severity of PVL in the majority of cases. In
PVL CLOSURE TECHNIQUES. Multimodality imaging
equivocal cases, invasive measurement of left ven-
guidance. Successful PVL closure relies heavily on
tricular and aortic pressures were used. In addition,
good understanding of the PVL anatomy. Meticulous
aortic root angiography was performed with grading
planning shortens the procedure time and increases
according to Sellers criteria in selected patients (15).
the chances of successful PVL reduction. The number, location(s), and severity of PVL defects were assessed
CLINICAL FOLLOW-UP. Procedural, in-hospital, and 30-
via detailed analysis of transthoracic echocardiograms
day outcomes were assessed by retrospective chart
and transesophageal echocardiograms, which were
review. Technical success was defined as successful
available in all patients (Figure 1). Additionally, later
deployment of a closure device across the leak with
in our experience we used electrocardiographically
reduction of the PVL to mild or less. Clinical success
gated cardiac computed tomography in the pre-
was defined as symptomatic improvement in NYHA
procedural assessment in selected patients. Cardiac
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 3 Illustration of the Commonly Applied Techniques in Aortic Paravalvular Leak Closure
(A) Catheter-only technique; (B) anchor wire technique; (C) arterioarterial rail technique. Abbreviations as in Figure 2.
computed tomography can be used to: 1) measure the
wire into the defect was difficult, a 6-F Amplatzer left 1
dimensions and identify the path of a PVL; 2) measure
guiding catheter (Boston Scientific, Marlborough,
the distance from the defect to the coronary ostium;
Massachusetts) was used as the second catheter of
and 3) identify the optimal fluoroscopic angles to cross
choice. Once the leak is crossed, 3 common techniques
the defect (Figure 2). Transesophageal echocardiog-
can be used to deliver the closure device: 1) a catheter-
raphy was used to guide the procedure when percu-
only technique; 2) an “anchor wire” technique; and 3)
taneous repair of a posterior leak(s) was planned or in
an arterioarterial rail technique.
cases of hemodynamic instability. Otherwise, the
The catheter-only technique (Figure 3A) is an
procedure was guided with transthoracic echocardi-
expeditious method that is useful when crossing of
ography or intracardiac echocardiography at the
the defect is smooth and the leak is likely to seal with
operator’s discretion.
1 device. After crossing the defect with the telescoped
PERCUTANEOUS PVL REPAIR. Anticoagulation was
system described earlier, the wire and the 5-F cath-
held and bridging with low–molecular weight heparin
eter are removed, and the device is advanced via the
was used in a minority of high-risk patients (e.g.,
6-F guiding catheter. A 6-F guide is compatible with
patients with double mechanical valves). In the vast
up to a 12-mm Amplatzer Vascular Plug II (AVPII, St.
majority of patients, 6-F arterial access was obtained
Jude Medical, St. Paul, Minnesota). If a larger AVPII
in the common femoral artery. Aortic PVL defects
device or other devices are needed, the guiding
were crossed with a 0.035-inch stiff angled Glide wire
catheter is exchanged over an Amplatzer extrastiff
(Terumo, Tokyo, Japan) through a telescoped 125-cm,
guidewire with a 6- or 7-F shuttle sheath (Cook
5-F multipurpose coronary catheter and a 6-F multi-
Medical, Bloomington, Indiana). A disadvantage of
purpose guiding catheter (Cordis Corporation, Hia-
this technique is the loss of guidewire position across
leah, Florida), respectively. If initial steering of the
the leak at the time of closure device deployment.
2419
2420
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
T A B L E 1 Key Baseline Characteristics of Patients Undergoing
T A B L E 2 Echocardiographic Findings in Patients Undergoing
Percutaneous Aortic Paravalvular Leak Closure (N ¼ 80)
Percutaneous Repair of Aortic Paravalvular Leak (N ¼ 80)
Age (yrs)
67.8 14.6
Male
56 (70)
Mild to moderate
3 (4)
Hypertension
71 (89)
Moderate
16 (20)
Diabetes
22 (28)
Severe
61 (76)
Obstructive coronary artery disease
47 (59)
LV ejection fraction
56 11
History of myocardial infarction
17 (21)
LV ejection fraction <40%
8 (10)
Peripheral arterial disease
24 (30)
LV end-diastolic diameter (mm)
56 7
Atrial fibrillation
37 (46)
LV end-systolic diameter (mm)
38 9
History of stroke
12 (15)
Right ventricular systolic pressure (mm Hg)
45 15
Mitral regurgitation
Baseline PVL grade
Chronic kidney disease stage $2
35 (44)
History of endocarditis
13 (16)
Mild or less
45 (69)
Chronic steroid
5 (6.3)
Moderate
18 (23)
Permanent pacemaker
23 (29)
Severe
7 (9)
Prior coronary bypass surgery
32 (40)
Tricuspid regurgitation
Number of prior sternotomies
1.4 0.9
Mild or less
48 (60)
Double mechanical valve
7 (9)
Moderate
17 (21)
Prior radiation
3 (4)
Severe
15 (19)
Reason for valve replacement
Mid thoracic aorta
36.4 6.0 20.5 10.6
Bicuspid aortic stenosis
22 (28)
Transaortic valve gradient
Tricuspid aortic stenosis
29 (36)
Number of defects
Endocarditis
7 (9)
1
55 (69)
Other
13 (16)
2
19 (24)
Tissue bioprosthesis
50 (63)
>2
6 (7)
Transcatheter heart valve
10 (12.5)
Location
Leak first detected (months)
22 40
Anterior
43 (54)
Implantation-to-repair time (months)
35 46
Posterior
20 (25)
Left-sided heart failure
66 (82.5)
Both
17 (21)
Right-sided heart failure
27 (34)
Hemolysis
17 (21.3)
Transfusion
8 (10)
Values are n (%) or mean SD. LV ¼ left ventricular; PVL ¼ paravalvular leak.
Indication for closure Heart failure
66 (82.5)
catheter. Therefore, the 6- to 8-F shuttle sheath is
Hemolysis
4 (5)
Both
10 (12.5)
advanced over the anchor wire and inside the 8-F
NYHA functional class
sheath across the defect. The operator should pay attention to the stiff tip of the dilator of the shuttle
#II
13 (16)
III
54 (68)
sheath to prevent left ventricular puncture or damage.
IV
13 (16)
The closure device is advanced alongside the anchor
5.7 4.6
wire into the left ventricle, is deployed across the
STS risk score Values are mean SD or n (%).
NYHA ¼ New York Heart Association; STS ¼ Society of Thoracic Surgeons.
defect, but remains attached to the delivery cable. The delivery catheter is then removed and placed back on the anchor wire only, leaving the device cable outside the delivery catheter. This remaining rail can
Recrossing of the leak is more challenging with an
be used to recross the defect if additional devices
existing device across the leak.
are needed, and if the operator fears losing access
The anchor wire technique (Figure 3B) preserves access across the defect and allows sequential
across the defect during attempts of closure device deployment.
deployment of multiple devices if necessary. In this
In rare occasions, a more stable rail is needed for
method, once the telescoping system is advanced in to
device deployment. In these cases, an arterioarterial
the left ventricle, the Glide wire is exchanged with an
rail technique (Figure 3C) can be used. The Glide wire
anchor wire (300-cm 0.032- or 0.035-inch Amplatzer
used to cross the defect is advanced through the aortic
extrastiff guidewire). The arterial sheath is then
valve into the descending aorta and is then snared and
upsized to a 45-cm 8- to 10-F bright-tip sheath (Cordis
exteriorized to the contralateral femoral artery,
Corporation) to minimize blood loss from the arterial
creating an arterioarterial rail. The reminder of the
site during catheter exchanges. The AVPII device does
procedure can be completed in a similar fashion to the
not fit alongside an anchor wire within a 6-F guiding
anchor wire steps. This technique can primarily be
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
2421
Percutaneous Aortic Paravalvular Leak Closure
T A B L E 3 Technical and Acute Procedural Data in
T A B L E 4 Univariate and Multivariate Logistic Regression of the Predictors of
86 Percutaneous Aortic Paravalvular Leak Repair
Procedural Technical Failure*
Procedures (N ¼ 86) Univariate
Urgent indication
8 (9.4)
Systolic blood pressure (mm Hg)
126 25
Diastolic blood pressure (mm Hg)
54 13
Pulse pressure (mm Hg)
72 23
General anesthesia
33 (38)
Imaging modality Intracardiac echocardiography
2 (2)
Transthoracic echocardiography
49 (57)
Transesophageal echocardiography
35 (41)
Number of defects attempted 1
67 (78)
2
18 (21)
$3
1 (1)
Number of defects closed 0
7 (8)
1
65 (76)
2
13 (15)
$3
1 (1)
OR
95% CI
Age, yrs
1.0
0.97–1.04
Multivariate p Value
OR
95% CI
0.77
1.03
0.97–1.09
Male
0.93
0.34–2.53
0.89
1.06
0.23–4.87
0.96
Diabetes
1.58
0.58–4.30
0.37
1.74
0.37–8.20
0.48
Bioprosthetic valve
0.54
0.21–1.37
0.19
0.30
0.05–1.76
0.18
TAVR
1.71
0.45–6.44
0.43
2.51
0.28–22.9
0.27
History of IE
7.83
0.004
15.2
2.2–104.5
0.006
Anterior leak
1.48
0.18
1.94
0.34–11.1
0.46
1.95–21.52 0.84–2.59
Urgent procedure
1.77
0.41–7.67
0.45
2.77
0.39–19.7
0.31
Transthoracic echocardiography
0.55
0.28–1.32
0.18
0.41
0.11–1.59
0.20
AVPII
1.13
0.43–2.94
0.80
1.16
0.24–5.59
0.85
More than 1 defect
3.66
1.36–9.83
0.01
4.01
0.90–17.9
0.069
LVEDD >60 mm
1.12
0.42–3.00
0.82
0.66
0.13–3.34
30 (35)
Apical rail
1 (1.2)
Successful procedure (device placed or not)
94 (90)
Number of devices placed
AVPII ¼ Amplatzer Vascular Plug II; CI ¼ confidence interval; IE ¼ infective endocarditis; LVEDD ¼ left ventricular end-diastolic dimension; OR ¼ odds ratio; TAVR ¼ transcatheter aortic valve replacement.
experience, an arterioapical rail was used in only 1 of 86 cases of aortic PVL closure.
1
55 (70)
2
15 (19)
$3
9 (11)
Important technical considerations
should
be
taken into account to maximize the efficiency and minimize the risks of the procedure.
Device types (AVPII vs. others) AVPII
61 (71)
First, device and sheath compatibility and fit
Other
16 (19)
are crucial to procedural execution. Knowledge of
AVPII plus others
2 (2)
sheath-sizing requirements for each device with and
Residual shunt
without an anchor wire shortens the duration and
None or trivial
22 (26)
Mild
31 (36)
Mild to moderate
17 (20)
Moderate or more
16 (19)
reduces the cost of the procedure. Compatibility charts are provided in Online Figure 1. Second, a feared complication of aortic PVL closure is the impingement of a mechanical or bioprosthetic
53 (62)
Procedural time (min)
86 46
valve leaflet during device deployment. Mechanical
Fluoroscopy time (min)
38 24
leaflet impingement is usually readily recognized with
Contrast load (ml)
46 58
fluoroscopy. However, impingement of bioprosthetic
Length of stay (days)
3.0 5.9
#48-h length of stay
leaflets, albeit rare, is more difficult to recognize but
69 (80)
can be suspected when there is echocardiographic evidence of sudden valvular regurgitation or an
Values are n (%) or mean SD.
increased transvalvular gradient. Detailed assessment
AVPI ¼ Amplatzer Vascular Plug II.
of valve leaflet motion should be performed in every case before releasing the closure device. In rare used in patients with bioprosthetic valves. Although
occasions, device interference with the prosthetic
we have used this technique successfully in patients
valve leaflets can occur after plug release because of
with mechanical prosthesis, we recommend against its
tilting of the device, which would require device
routine use with mechanical valves. A wire across the
removal with a snare or a long, flexible bioptome.
mechanical valve can lead to stuck leaflets with severe
Third, para-aortic leak closure may lead to coro-
aortic regurgitation and result in rapid hemodynamic
nary artery obstruction. Aortography or selective
compromise. If the patient has a mechanical valve and
coronary angiography may be needed to assess ostial
the device could not be delivered without a rail, the left
clearance before device release. Meticulous cardiac
ventricular wire can be snared through a transseptal or
computed tomographic measurement and analyses
transapical puncture, creating an arteriovenous rail
can identify low takeoff of the left or right coronary
and
ostia before the procedure.
an
arterioapical
rail,
respectively.
In
0.62
*Defined as more than mild residual leak at the end of the procedure.
Double or anchor wire
Mild or less
p Value
0.35
our
2422
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 4 Change in New York Heart Association Functional Class at 30 Days After
Aortic Paravalvular Leak Closure
greater than mild). The probability of death or repeat surgery according to residual PVL groups was graphically displayed according to the method of Kaplan and Meier, with comparison of cumulative survival across strata by the log-rank test. Binary logistic regression analysis was used to identify variables independently associated with the failure to reduce the PVL to less than mild (technical failure). Variables included in the model were age, sex, diabetes, prosthesis type (bioprosthesis vs. mechanical, transcatheter heart valve), history of infective endocarditis (IE), location of the PVL, procedure status (elective vs. urgent), imaging guidance (transthoracic vs. transesophageal echocardiography), and device type (AVPII vs. others). All analyses were performed with SPSS version 22 (IBM, Armonk, New York). Statistical significance was inferred at p #0.05.
RESULTS STUDY COHORT. Eighty-six aortic PVL closure pro-
cedures were performed in 80 patients. Baseline characteristics of the study population are shown in Table 1. The mean age was 67.8 14.6 years, 70% were men, and 63% had bioprosthetic valves. The mean number of prior sternotomies was 1.4 0.9 (range 0 to 6). The indication for aortic valve replacement was calcific aortic stenosis in 64%, IE in 9%, aortic regurgitation in 6%, and rheumatic aortic valve disease in 5%. The primary indication for percutaneous PVL (A) New York Heart Association (NYHA) functional class change overall and according to
closure was symptoms of heart failure in 66 patients
the residual leak. (B) Distribution of NYHA functional class before and after paravalvular
(83%), hemolysis in 4 patients (5%), and both in 10
leak closure.
patients (12%). Eight procedures (9.4%) were done urgently in patients not in stable condition who presented with decompensated heart failure soon after STUDY ENDPOINTS. The primary efficacy endpoints
aortic valve replacement. The mean times from valve
of the study were the change in NYHA functional class
implantation to first detection of aortic PVL and to
at 30 days and the elimination of transfusion
percutaneous repair were 22 40 months and 35 46
requirement
hemolysis
months, respectively. Using the Society of Thoracic
requiring blood transfusion. The primary safety
Surgeons risk calculator, the estimated operative
endpoint of the study was the occurrence of acute and
mortality for open repair in the cohort was 5.7 4.6.
in
patients
with
severe
30-day major adverse cardiovascular events, defined as stroke, major vascular complications, tamponade, acute coronary syndrome, or death. Secondary endpoints were: 1) long-term survival from death within the duration of the study; and 2) long-term event-free freedom from repeat cardiac surgery. DATA
ANALYSIS. Continuous
ACUTE PROCEDURAL OUTCOMES. Echocardiographic
guidance was used in all cases. Baseline echocardiographic data are summarized in Table 2. Percutaneous repair was attempted in a total of 105 PVLs in 80 patients. Successful crossing and device deployment were achieved in 94 defects using 114 closure
parameters of the
devices (90%). The AVPII device was used in the ma-
study groups were compared using the Student t test.
jority of cases (88%). The reasons for failure to close the
For comparison of categorical data, we used the
11 remaining leaks were inability to cross the defect
chi-square or Fisher exact test. To examine the impact
with a wire or with a sheath in 8 defects, impingement
of residual regurgitation on outcomes, patients were
of prosthetic leaflet in 1, proximity to a coronary artery
grouped according to the residual PVL (mild or less,
ostium in 1, and coronary dissection in 1.
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
Technical success (defined as mild or less residual PVL) was achieved in 53 patients (62%). The residual
T A B L E 5 Short-Term (30 Days) and Long-Term Clinical
Outcomes of Patients Who Underwent Percutaneous Aortic
PVLs were mild to moderate in 17 patients (20%)
Paravalvular Leak Closure (N ¼ 80)
and
In-hospital outcomes
moderate
or
more
in
16
patients
(18%)
(Table 3). Among multiple baseline and procedural
MACE
6 (7.6)
characteristics, only history of IE predicted more than
Death
2 (2.5)
mild residual PVL after the procedure (Table 4).
Procedure-related death
1 (1.3)
In-hospital major
adverse
cardiovascular
events
occurred in 6 patients (7.6%). These included death in 2 (2.5%) (1 due to tamponade and hemothorax after an apical puncture and 1 due to persistent cardiogenic
30-day outcomes MACE
10 (12.5)
Death
5 (6.3)
Mean change in NYHA functional class
0.94 0.72
NYHA functional class
shock in a patient who underwent successful salvage
I
19 (27.0)
PVL closure immediately after surgical aortic valve
II
32 (46.0)
replacement), stroke in 1 (1.2%), retroperitoneal
III
16 (23.0)
bleeding in 1 (1.2%), tamponade in 1 (1.2%), and cor-
IV
3 (4.0)
onary dissection in 1 (1.2%). The mean length of
Died or missing
10
hospital stay was 2.3 3.2 days for patients who un-
Elimination of transfusion requirements
7 (88.0)
derwent elective PVL closure compared with 10.8 15.7
days
for
patients
who
underwent
urgent
procedures (p < 0.001). SHORT-TERM (30-DAY) OUTCOMES. C l i n i c a l e f fi c a c y .
Clinical follow-up (NYHA functional class assessment) at 30 days was available in 70 patients (93%).
Long-term outcomes Mean follow-up (months)
27 25
Death
22 (27.5)
Redo valve replacement
10 (13.0)
Repeat percutaneous closure
5 (6.3)
CHF readmission
18 (23.0)
Stroke
5 (6.0)
NYHA functional class at maximum follow up
The primary endpoint of the study was achieved in
I
19 (24.0)
51 patients (64%). The mean change in NYHA func-
II
24 (30.0)
tional class was 0.9 0.5 (Figure 4). Patients who
III
18 (23.0)
had successful reductions in PVL grade to mild or less experienced significantly more improvement in NYHA functional class (mean change 1.21, from 2.93
Values are n (%) or mean SD. CHF ¼ congestive heart failure; MACE ¼ major adverse cardiovascular event(s); NYHA ¼ New York Heart Association.
0.62 to 1.72 0.73) compared with those with more than mild residual leak (mean change 0.51, from 3.03 0.57 to 2.52 0.74) (p < 0.001) (Figure 4). In patients with severe hemolysis requiring blood
follow-up, all-cause mortality was 27.5%, and redo
transfusion (n ¼ 8), transfusion requirement was
valve replacement for residual or recurrent PVL was
eliminated in 7 cases (88%).
13% (Table 5). Compared with patients who had more
o u t c o m e s . Among the 78 patients dis-
than mild post-procedure leak, those who had mild or
charged from the hospital, 5 major adverse cardio-
less residual leak had better freedom from repeat
vascular events occurred in 4 patients (5.1%): 3 deaths
cardiac surgery but long-term survival rates were
Safety
and 2 hemorrhagic strokes. Two deaths occurred after
similar (Figure 5). In patients who achieved event-free
successful PVL closure; 1 was at day 6 because of a
survival, the initial improvement in NYHA functional
hemorrhagic stroke, and 1 was at day 27 because of an
class persisted at maximum follow-up (mean NYHA
unknown cause in a 35 year-old patient with a 27-mm
functional class 1.95 0.78). The magnitude of
Starr-Edwards Silastic Ball valve. One death occurred
NYHA functional class improvement was more sig-
at day 28 because of decompensated heart failure
nificant in patients with mild or less residual leak
after an unsuccessful attempt for PVL closure in an
(mean NYHA functional class 1.76 0.74 vs. 2.24
86-year-old patient with a 23-mm SAPIEN-XT valve.
0.76; p ¼ 0.027).
Both hemorrhagic strokes occurred between 2 and 5 days after the procedure in patients who were bridged to therapeutic warfarin with low–molecular weight heparin.
DISCUSSION The principal findings of the present investigation are
LONG-TERM OUTCOMES. Median follow-up for the
as follows. 1) Percutaneous repair of aortic PVL can
study patients was 18.5 months, with a range of
be performed safely with a low incidence of major
1 to 101 months (mean 27 25 months). During
complications. 2) Cannulation and closure device
2423
2424
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 5 Kaplan-Meier Curves Showing Survival Free of Death and
Repeat Cardiac Surgery According to Degree of Residual Paravalvular Leak
PVL is seen predominantly in patients with moderate and severe PVL (17,18). We classified successful PVL closure on the basis of the residual leak to mild or less (technical success) and more than mild (technical failure). Similar to what has been observed in the post-TAVR PVL literature, our findings suggest that more
than
mild
residual
PVL
after
percutan-
eous closure is associated with less symptomatic improvement and a lower rate of event-free survival. Although there was no difference in all-cause mortality between the 2 groups, our study is underpowered to detect mortality differences given the small sample size. Achieving complete or near complete obliteration of aortic PVL, however, can be challenging. As illustrated in this study, although successful crossing of aortic PVL and deployment of closure device(s) across the leaks were achieved in 90% of defects, reduction in PVL to mild or less was possible in only 62% of patients. This can be due to a number of reasons. First, a significant predictor of more than mild residual PVL in this study was a history of IE. The process of inflammation and healing in IE can lead to scar formation and/or fibrosis and may result in tissue fragility, which can make complete abolition of the leak more challenging. Other predictors of technical failure are the presence of mechanical prostheses,
transcatheter
heart
valve,
and
urgent
indications for PVL closure. Bioprosthetic valves generally have lower risk for device-leaflet interaction. In contrast, the spatial relationship of mechanical prosthesis occluder discs relative to the defect(s) is a key determinant of the size and number of devices that can be implanted without leaflet impingement. Therefore, technical success rates are expected to be lower with mechanical prostheses (11). Patients who develop significant PVL after PVL ¼ paravalvular leak.
TAVR represent another challenging group. In these patients, if the transcatheter heart valve is properly positioned and adequately expanded, the PVL is due
deployment across aortic PVL was achieved in the
to the lack of surgical excision of the old calcified
vast majority of PVLs (90%). However, successful
valve, resulting in multiple defects of small dimen-
reduction of the PVL to mild or less was only achieved
sions (19). Smaller profile devices such as the
in 62% of patients. 3) History of IE was strongly
Amplatzer Vascular Plug IV have been used in these
correlated with significant residual leak after percu-
patients, but the technical success rate has been
taneous PVL closure. 4) Successful PVL reduction to
only modest (20–22).
mild or less resulted in quick and durable symptom-
Second, despite the growing prevalence of PVL,
atic relief and reduced the need for redo cardiac
there are no devices that were designed, tested, or
surgery.
approved for PVL closure (23). The AVPII is the most
There is growing evidence from the global experi-
commonly used off-label device because of its sta-
ence with transcatheter aortic valve replacement
bility and low profile. However, many patients
(TAVR) that PVL after TAVR is associated with poor
have crescentic or irregular shaped PVLs, and the
long-term outcomes. However, the negative impact of
AVPII may not be adequate for treatment of such
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
defects (24). In recent years, the Amplatzer Vascular
Third, residual PVL grade in our study was corre-
Plug III has been increasingly used for PVL closure
lated with symptomatic improvement and need for
given its oblong shape (25,26). Also, a new purpose-
redo surgery. However, grading of aortic PVL can be
specific device, the Occlutech PLD occluder (Occlu-
quite challenging. Echocardiographic measures used
tech, Jena, Germany), was designed to tackle a large
to grade PVL are semiquantitative and suffer from
range of PVL sizes and morphologies (26). Early
limited validation. This could lead to interpretation
experience with the Occlutech PLD device showed
variability, which may affect the results of this study.
results (26,27). Unfortunately,
Fourth, follow-up laboratory data on patients with
neither the Amplatzer Vascular Plug III nor the
hemolysis were limited because of the referral nature
Occlutech is available in the United States. Another
of our center. However, in those with severe hemo-
consideration to increase the success rate of the
lysis requiring blood transfusion, PVL closure elimi-
procedure is the possible use of transapical access in
nated blood transfusion in all but 1 patient.
very encouraging
selected cases. Transapical access has been used pri-
Last, the small number of patients enrolled in this
marily in the treatment of mitral PVL for medial and
study may affect the reliability of the data, and the
anterior leaks or when concomitant aortic and mitral
validity of certain statistical analyses (e.g., logistical
PVL closure is planned (12). Although transapical ac-
regressions). However, to our knowledge this is the
cess is potentially associated with higher complica-
largest reported series of percutaneous aortic PVL
tion rates, these can be minimized by careful access
closure. The descriptive data in our study are very
planning with a pre-acquired computed tomographic
valuable in closing the knowledge gap on the
angiogram and closure of the access site with vascular
management of this complex entity.
plugs or occluders (12). Despite the low rate of adverse events in our series, further modification of the current technique
CONCLUSIONS
may further lower the risk for these complications.
Percutaneous aortic PVL closure can be performed
First, we observed 2 hemorrhagic strokes in patients
with high technical success and low complication
with atrial fibrillation who were bridged with low–
rates. Successful PVL reduction to mild or less results
molecular weight heparin. Recently, the BRIDGE
in quick and durable symptomatic relief and reduces
(Bridging Anticoagulation in Patients Who Require
the need for redo cardiac surgery. Attempts should be
Temporary Interruption of Warfarin Therapy for an
made to accomplish adequate reduction in PVL to
Elective Invasive Procedure or Surgery) trial sug-
optimize clinical outcomes.
gested no benefit and higher bleeding events in patients who underwent periprocedural bridging
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
with low–molecular weight heparin for atrial fibril-
Charanjit S. Rihal, Mayo Clinic College of Medicine,
lation (28). Therefore, we believe that bridging
Division of Cardiovascular Diseases, 200 First Street
anticoagulation should be avoided when possible.
SW, Rochester, Minnesota 55905. E-mail: rihal@
Second, a meticulous post-procedural protocol that
mayo.edu.
includes frequent echocardiographic examinations should be implemented when an apical puncture is
PERSPECTIVES
performed to aid in early detection and management of hemothorax or tamponade. Closing the apical puncture site with a vascular plug should also be considered when sheath sizes >4 F are used. STUDY LIMITATIONS. First, the retrospective nature
of this study has known limitations, including potential for referral basis. Notably, serial echocardiography was not performed, and data on residual regurgitation at final follow-up were not available, because of the referral nature of our clinical practice. Second, the practice of PVL closure might differ outside the United States because of the availability of purpose-specific devices. Therefore, the results of this study may not be generalizable to practices outside the United States.
WHAT IS KNOWN? Percutaneous closure has emerged as an alternative therapy to repeat valve surgery for patients with symptomatic aortic PVL. However, procedural and long-term outcomes of percutaneous closure techniques are not known. WHAT IS NEW? Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to grade mild or less, which was achieved in two-thirds of the patients. WHAT IS NEXT? Further studies are needed to assess the effectiveness of PVL closure with purpose-specific devices.
2425
2426
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
REFERENCES 1. Miller DL, Morris JJ, Schaff HV, Mullany CJ, Nishimura RA, Orszulak TA. Reoperation for aortic valve periprosthetic leakage: identification of patients at risk and results of operation. J Heart Valve Dis 1995;4:160–5. 2. Hwang HY, Choi JW, Kim HK, Kim KH, Kim KB, Ahn H. Paravalvular leak after mitral valve replacement: 20-year follow-up. Ann Thorac Surg 2015;100:1347–52. 3. Davila-Roman VG, Waggoner AD, Kennard ED, et al. Prevalence and severity of paravalvular regurgitation in the Artificial Valve Endocarditis Reduction Trial (AVERT) echocardiography study. J Am Coll Cardiol 2004;44:1467–72.
closure of periprosthetic paravalvular leaks. J Am Coll Cardiol 2011;58:2210–7. 13. Cho IJ, Moon J, Shim CY, et al. Different clinical outcome of paravalvular leakage after aortic or mitral valve replacement. Am J Cardiol 2011;107: 280–4. 14. Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of prosthetic valves with echocardiography and Doppler ultrasound: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging
4. Akins CW, Bitondo JM, Hilgenberg AD, Vlahakes GJ, Madsen JC, MacGillivray TE. Early and late results of the surgical correction of cardiac prosthetic paravalvular leaks. J Heart Valve Dis 2005;14:792–9.
Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, endorsed by the
5. Taramasso M, Maisano F, Denti P, et al. Surgical treatment of paravalvular leak: Long-term results in a single-center experience (up to 14 years). J Thorac Cardiovasc Surg 2015;149:1270–5.
American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography. J Am Soc Echocardiogr
6. Genoni M, Franzen D, Vogt P, et al. Paravalvular leakage after mitral valve replacement: improved long-term survival with aggressive surgery? Eur J Cardiothorac Surg 2000;17:14–9. 7. Orszulak TA, Schaff HV, Danielson GK, Pluth JR, Puga FJ, Piehler JM. Results of reoperation for periprosthetic leakage. Ann Thorac Surg 1983;35: 584–9. 8. Millan X, Skaf S, Joseph L, et al. Transcatheter reduction of paravalvular leaks: a systematic review and meta-analysis. Can J Cardiol 2015;31: 260–9. 9. Smolka G, Pysz P, Jasinski M, et al. Multiplug paravalvular leak closure using Amplatzer Vascular Plugs III: a prospective registry. Catheter Cardiovasc Interv 2016;87:478–87. 10. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Long-term follow-up of percutaneous repair of paravalvular prosthetic regurgitation. J Am Coll Cardiol 2011;58:2218–24. 11. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Percutaneous repair of paravalvular prosthetic regurgitation: acute and 30-day outcomes in 115 patients. Circ Cardiovasc Interv 2011;4:314–21. 12. Ruiz CE, Jelnin V, Kronzon I, et al. Clinical outcomes in patients undergoing percutaneous
2009;22:975–1014. 15. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease: technic, indications and interpretations in 700 cases. Am J Cardiol 1964; 14:437–47. 16. National Center for Health Statistics. National Death Index User’s Guide. Available at: https:// www.cdc.gov/nchs/data/ndi/ndi_users_guide.pdf. Accessed September 8, 2016. 17. Jerez-Valero M, Urena M, Webb JG, et al. Clinical impact of aortic regurgitation after transcatheter aortic valve replacement: insights into the degree and acuteness of presentation. J Am Coll Cardiol Intv 2014;7:1022–32. 18. Athappan G, Patvardhan E, Tuzcu EM, et al. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: meta-analysis and systematic review of literature. J Am Coll Cardiol 2013;61:1585–95. 19. Eleid MF, Cabalka AK, Malouf JF, Sanon S, Hagler DJ, Rihal CS. Techniques and outcomes for the treatment of paravalvular leak. Circ Cardiovasc Interv 2015;8:e001945.
20. Gafoor S, Franke J, Piayda K, et al. Paravalvular leak closure after transcatheter aortic valve replacement with a self-expanding prosthesis. Catheter Cardiovasc Interv 2014;84: 147–54. 21. Feldman T, Salinger MH, Levisay JP, Smart S. Low profile vascular plugs for paravalvular leaks after TAVR. Catheter Cardiovasc Interv 2014;83: 280–8. 22. Okuyama K, Jilaihawi H, Kashif M, et al. Percutaneous paravalvular leak closure for balloon-expandable transcatheter aortic valve replacement: a comparison with surgical aortic valve replacement paravalvular leak closure. J Invasive Cardiol 2015;27:284–90. 23. Kim MS, Casserly IP, Garcia JA, Klein AJ, Salcedo EE, Carroll JD. Percutaneous transcatheter closure of prosthetic mitral paravalvular leaks: are we there yet? J Am Coll Cardiol Intv 2009;2:81–90. 24. McElhinney DB. Will there ever be a Food and Drug Administration–approved device for transcatheter paravalvular leak closure? Circ Cardiovasc Interv 2014;7:2–5. 25. Cruz-Gonzalez I, Rama-Merchan JC, ArribasJimenez A, et al. Paravalvular leak closure with the Amplatzer Vascular Plug III device: immediate and short-term results. Rev Esp Cardiol (Engl Ed) 2014;67:608–14. 26. Bedair R, Morgan GJ, Bapat V, et al. Early experience with the Occlutech PLD occluder for mitral paravalvar leak closure through a hybrid transapical approach. EuroIntervention 2015;11. 20150419–01. 27. Yildirim A, Goktekin O, Gorgulu S, et al. A new specific device in transcatheter prosthetic paravalvular leak closure: a prospective two-center trial. Catheter Cardiovasc Interv 2016; 88:618–24. 28. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373: 823–33.
KEY WORDS aortic regurgitation, paravalvular leak, percutaneous repair A PPE NDI X For a supplemental figure, please see the online version of this article.
VOL. 9, NO. 23, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-8798/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jcin.2016.08.038
STRUCTURAL
Techniques and Outcomes of Percutaneous Aortic Paravalvular Leak Closure Mohamad Alkhouli, MD, Mohammad Sarraf, MD, Elad Maor, MD, Saurabh Sanon, MBBS, Allison Cabalka, MD, Mackram F. Eleid, MD, Donald J. Hagler, MD, Peter Pollak, MD, Guy Reeder, MD, Charanjit S. Rihal, MD
ABSTRACT OBJECTIVES The aim of this study is to provide a summary of the currently applied aortic paravalvular leak (PVL) closure techniques and describe the procedural and long-term outcomes in a large consecutive cohort of patients. BACKGROUND Percutaneous repair has emerged as an effective therapy for patients with PVL. To date, clinical outcome data on percutaneous closure of aortic PVL are limited. METHODS All patients who underwent catheter-based treatment of aortic PVL between 2006 and 2015 were identified. Procedural and short-term results were assessed. Patients were contacted for clinical events and symptoms. RESULTS Eighty-six procedures were performed in 80 patients. The mean age was 68 15 years, and 70% were men. The primary indications for PVL closure were symptoms of heart failure, hemolysis, and both in 83%, 5%, and 12%, respectively. Successful device deployment was accomplished in 94 defects (90%). Reduction in PVL to mild or less was achieved in 62% of patients. In-hospital major adverse events occurred in 8% of procedures. Symptomatic improvement at 30 days was achieved in 64% of patients. Patients who had reduction in the PVL grade to mild or less experienced more improvement in New York Heart Association functional class (from 2.93 0.62 to 1.72 0.73) compared with those with mild or greater residual leak (from 3.03 0.57 to 2.52 0.74) (p < 0.001). In patients with severe hemolysis (n ¼ 8), transfusion requirements were eliminated in 7 (88%) after PVL closure. Kaplan-Meier survival analysis showed that the cumulative probability of freedom from repeat surgery at 2 years was 98 2% in patients who had mild or less residual leak compared with 68 10% in patients with higher grades of residual PVL (log-rank p ¼ 0.004). CONCLUSIONS Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to a grade of mild or less. Therefore, attempts should be made to reduce PVL as much as possible. (J Am Coll Cardiol Intv 2016;9:2416–26) © 2016 by the American College of Cardiology Foundation.
P
aravalvular leak (PVL) occurs in 5% to 17% of patients
after
valve
replacement
Percutaneous repair has emerged as an effective ther-
surgery
apy for patients with PVL, with feasibility and efficacy
(1–4). For symptomatic patients, repeat sur-
demonstrated in multiple studies (8–12). Although the
gery has been the traditional treatment of choice,
principles of transcatheter closure of mitral and aortic
but it is associated with high operative mortality and
PVL are similar, the techniques and procedural
variable results even in the modern era (1,4–7).
complexity differ significantly (13). Mitral PVL closure
From the Divisions of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 21, 2016; revised manuscript received August 22, 2016, accepted August 25, 2016.
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
2417
Percutaneous Aortic Paravalvular Leak Closure
is more intricate than aortic PVL because of some
(Rochester, Minnesota) before January 10,
ABBREVIATIONS
procedural and leak-specific characteristics. To date,
2016. The indications for percutaneous repair
AND ACRONYMS
the largest series examining the outcomes of percuta-
were moderate or severe PVL with severe or
neous PVL closure included only a small number of
life-style-limiting dyspnea (New York Heart
patients with aortic PVL (10,12,13).
Association [NYHA] functional class III or IV
AVPII = Amplatzer Vascular Plug II
IE = infective endocarditis
We hypothesized that aortic PVL closure can be
or class II with significant life-style or occu-
achieved with high success and low complications
pational impairment) or clinically significant
rates and that the degree of PVL reduction correlates
hemolytic anemia. Patients who had active
with symptomatic improvement and clinical out-
endocarditis and those who had large leaks
comes. In this report, we review the commonly
involving more than one-half of the circum-
applied techniques in aortic PVL closure and provide
ference of the sewing ring, or rocking motion
comprehensive data on the procedural and long-term
of the valve, were referred for surgical repair. Clini-
NYHA = New York Heart Association
PVL = paravalvular leak TAVR = transcatheter aortic valve replacement
outcomes of a large consecutive cohort of patients
cally significant hemolytic anemia was defined as
referred for aortic PVL closure.
symptomatic anemia (hemoglobin <11 g/dl in women
SEE PAGE 2427
METHODS
and <12.5 g/dl in men), with laboratory evidence of intravascular hemolysis. GRADING OF AORTIC PVL. The assessment of the
severity of aortic PVL incorporated a multifaceted STUDY POPULATION. The Mayo Clinic Institutional
approach. This included echocardiographic, invasive
Review Board approved this investigation. We retro-
hemodynamic, and angiographic measures. Semi-
spectively identified patients who underwent percu-
quantitative echocardiographic parameters were used
taneous repair of aortic PVL at the Mayo Clinic
in all cases to grade the PVL as mild, mild to
F I G U R E 1 Utility of Echocardiography in Aortic Paravalvular Leak Closure
Transeophageal echocardiography (TEE) revealing significant para-aortic leak in 2 patients (Patient#1, A, B) and (Patient#2, C to F). (A) Moderate posterior para-aortic leak pre-closure (arrow). (B) Trivial residual leak after deployment with a 12-mm Amplatzer Vascular Plug II (AVPII) device (arrow). The star indicates the delivery cable before device release. (C) 3-dimensional TEE showing severe anteriomedial para-aortic leak pre-closure (arrow). (D) 3-dimensional TEE showing successful closure of the leak with 3 AVPII devices (arrow). (E) 3D-dimensional TEE in the same patient showing an interval development of a de novo leak at a different anterior location 9 months after the index procedure. (F) 3D-dimensional TEE showing successful closure of the leak with 1 AVPII device (dashed arrow). The plugs from the prior closure procedure are indicated by the arrow.
2418
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 2 Utility of Cardiac Computed Tomography in the Pre-Procedural Planning of Aortic Paravalvular Leak Closure
(A to C) Identification of the location and dimensions of an aortic paravalvular leak on cardiac computed tomography. The paravalvular leak can be readily located in a modified 4-chamber view (A), a modified 2-chamber view (B), and a modified short-axis views (C) (yellow arrows). The distance between the neck of the paravalvular leak and the ostium of the adjacent coronary artery is shown in D. The black star indicates the ostium of the left main coronary artery. AO ¼ aorta; LA ¼ left atrium; LV ¼ left ventricle.
moderate, moderate, or severe: 1) the PVL jet width
functional class by at least 1 class and/or elimination
(vena contracta) measured in the short- and long-axis
of need for transfusion in cases of severe hemolysis.
views at the level of the prosthesis sewing ring and in
Patients were contacted by telephone survey to
the left ventricular outflow tract; 2) assessment of
determine occurrence of adverse events, symptoms,
diastolic flow reversal in the descending thoracic and
and clinical status. In addition, the dates of death of
abdominal aorta; and 3) measurement of deceleration
deceased patients were verified by querying the
rate by pressure half-time (14). In the presence of
National Death Index, a centralized database of death
multiple defects, the sum of regurgitation from these
record information on file in state vital statistics
defects was used. Quantitative Doppler parameters
offices (16).
(e.g., regurgitant volume) were also used to confirm the severity of PVL in the majority of cases. In
PVL CLOSURE TECHNIQUES. Multimodality imaging
equivocal cases, invasive measurement of left ven-
guidance. Successful PVL closure relies heavily on
tricular and aortic pressures were used. In addition,
good understanding of the PVL anatomy. Meticulous
aortic root angiography was performed with grading
planning shortens the procedure time and increases
according to Sellers criteria in selected patients (15).
the chances of successful PVL reduction. The number, location(s), and severity of PVL defects were assessed
CLINICAL FOLLOW-UP. Procedural, in-hospital, and 30-
via detailed analysis of transthoracic echocardiograms
day outcomes were assessed by retrospective chart
and transesophageal echocardiograms, which were
review. Technical success was defined as successful
available in all patients (Figure 1). Additionally, later
deployment of a closure device across the leak with
in our experience we used electrocardiographically
reduction of the PVL to mild or less. Clinical success
gated cardiac computed tomography in the pre-
was defined as symptomatic improvement in NYHA
procedural assessment in selected patients. Cardiac
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 3 Illustration of the Commonly Applied Techniques in Aortic Paravalvular Leak Closure
(A) Catheter-only technique; (B) anchor wire technique; (C) arterioarterial rail technique. Abbreviations as in Figure 2.
computed tomography can be used to: 1) measure the
wire into the defect was difficult, a 6-F Amplatzer left 1
dimensions and identify the path of a PVL; 2) measure
guiding catheter (Boston Scientific, Marlborough,
the distance from the defect to the coronary ostium;
Massachusetts) was used as the second catheter of
and 3) identify the optimal fluoroscopic angles to cross
choice. Once the leak is crossed, 3 common techniques
the defect (Figure 2). Transesophageal echocardiog-
can be used to deliver the closure device: 1) a catheter-
raphy was used to guide the procedure when percu-
only technique; 2) an “anchor wire” technique; and 3)
taneous repair of a posterior leak(s) was planned or in
an arterioarterial rail technique.
cases of hemodynamic instability. Otherwise, the
The catheter-only technique (Figure 3A) is an
procedure was guided with transthoracic echocardi-
expeditious method that is useful when crossing of
ography or intracardiac echocardiography at the
the defect is smooth and the leak is likely to seal with
operator’s discretion.
1 device. After crossing the defect with the telescoped
PERCUTANEOUS PVL REPAIR. Anticoagulation was
system described earlier, the wire and the 5-F cath-
held and bridging with low–molecular weight heparin
eter are removed, and the device is advanced via the
was used in a minority of high-risk patients (e.g.,
6-F guiding catheter. A 6-F guide is compatible with
patients with double mechanical valves). In the vast
up to a 12-mm Amplatzer Vascular Plug II (AVPII, St.
majority of patients, 6-F arterial access was obtained
Jude Medical, St. Paul, Minnesota). If a larger AVPII
in the common femoral artery. Aortic PVL defects
device or other devices are needed, the guiding
were crossed with a 0.035-inch stiff angled Glide wire
catheter is exchanged over an Amplatzer extrastiff
(Terumo, Tokyo, Japan) through a telescoped 125-cm,
guidewire with a 6- or 7-F shuttle sheath (Cook
5-F multipurpose coronary catheter and a 6-F multi-
Medical, Bloomington, Indiana). A disadvantage of
purpose guiding catheter (Cordis Corporation, Hia-
this technique is the loss of guidewire position across
leah, Florida), respectively. If initial steering of the
the leak at the time of closure device deployment.
2419
2420
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
T A B L E 1 Key Baseline Characteristics of Patients Undergoing
T A B L E 2 Echocardiographic Findings in Patients Undergoing
Percutaneous Aortic Paravalvular Leak Closure (N ¼ 80)
Percutaneous Repair of Aortic Paravalvular Leak (N ¼ 80)
Age (yrs)
67.8 14.6
Male
56 (70)
Mild to moderate
3 (4)
Hypertension
71 (89)
Moderate
16 (20)
Diabetes
22 (28)
Severe
61 (76)
Obstructive coronary artery disease
47 (59)
LV ejection fraction
56 11
History of myocardial infarction
17 (21)
LV ejection fraction <40%
8 (10)
Peripheral arterial disease
24 (30)
LV end-diastolic diameter (mm)
56 7
Atrial fibrillation
37 (46)
LV end-systolic diameter (mm)
38 9
History of stroke
12 (15)
Right ventricular systolic pressure (mm Hg)
45 15
Mitral regurgitation
Baseline PVL grade
Chronic kidney disease stage $2
35 (44)
History of endocarditis
13 (16)
Mild or less
45 (69)
Chronic steroid
5 (6.3)
Moderate
18 (23)
Permanent pacemaker
23 (29)
Severe
7 (9)
Prior coronary bypass surgery
32 (40)
Tricuspid regurgitation
Number of prior sternotomies
1.4 0.9
Mild or less
48 (60)
Double mechanical valve
7 (9)
Moderate
17 (21)
Prior radiation
3 (4)
Severe
15 (19)
Reason for valve replacement
Mid thoracic aorta
36.4 6.0 20.5 10.6
Bicuspid aortic stenosis
22 (28)
Transaortic valve gradient
Tricuspid aortic stenosis
29 (36)
Number of defects
Endocarditis
7 (9)
1
55 (69)
Other
13 (16)
2
19 (24)
Tissue bioprosthesis
50 (63)
>2
6 (7)
Transcatheter heart valve
10 (12.5)
Location
Leak first detected (months)
22 40
Anterior
43 (54)
Implantation-to-repair time (months)
35 46
Posterior
20 (25)
Left-sided heart failure
66 (82.5)
Both
17 (21)
Right-sided heart failure
27 (34)
Hemolysis
17 (21.3)
Transfusion
8 (10)
Values are n (%) or mean SD. LV ¼ left ventricular; PVL ¼ paravalvular leak.
Indication for closure Heart failure
66 (82.5)
catheter. Therefore, the 6- to 8-F shuttle sheath is
Hemolysis
4 (5)
Both
10 (12.5)
advanced over the anchor wire and inside the 8-F
NYHA functional class
sheath across the defect. The operator should pay attention to the stiff tip of the dilator of the shuttle
#II
13 (16)
III
54 (68)
sheath to prevent left ventricular puncture or damage.
IV
13 (16)
The closure device is advanced alongside the anchor
5.7 4.6
wire into the left ventricle, is deployed across the
STS risk score Values are mean SD or n (%).
NYHA ¼ New York Heart Association; STS ¼ Society of Thoracic Surgeons.
defect, but remains attached to the delivery cable. The delivery catheter is then removed and placed back on the anchor wire only, leaving the device cable outside the delivery catheter. This remaining rail can
Recrossing of the leak is more challenging with an
be used to recross the defect if additional devices
existing device across the leak.
are needed, and if the operator fears losing access
The anchor wire technique (Figure 3B) preserves access across the defect and allows sequential
across the defect during attempts of closure device deployment.
deployment of multiple devices if necessary. In this
In rare occasions, a more stable rail is needed for
method, once the telescoping system is advanced in to
device deployment. In these cases, an arterioarterial
the left ventricle, the Glide wire is exchanged with an
rail technique (Figure 3C) can be used. The Glide wire
anchor wire (300-cm 0.032- or 0.035-inch Amplatzer
used to cross the defect is advanced through the aortic
extrastiff guidewire). The arterial sheath is then
valve into the descending aorta and is then snared and
upsized to a 45-cm 8- to 10-F bright-tip sheath (Cordis
exteriorized to the contralateral femoral artery,
Corporation) to minimize blood loss from the arterial
creating an arterioarterial rail. The reminder of the
site during catheter exchanges. The AVPII device does
procedure can be completed in a similar fashion to the
not fit alongside an anchor wire within a 6-F guiding
anchor wire steps. This technique can primarily be
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
2421
Percutaneous Aortic Paravalvular Leak Closure
T A B L E 3 Technical and Acute Procedural Data in
T A B L E 4 Univariate and Multivariate Logistic Regression of the Predictors of
86 Percutaneous Aortic Paravalvular Leak Repair
Procedural Technical Failure*
Procedures (N ¼ 86) Univariate
Urgent indication
8 (9.4)
Systolic blood pressure (mm Hg)
126 25
Diastolic blood pressure (mm Hg)
54 13
Pulse pressure (mm Hg)
72 23
General anesthesia
33 (38)
Imaging modality Intracardiac echocardiography
2 (2)
Transthoracic echocardiography
49 (57)
Transesophageal echocardiography
35 (41)
Number of defects attempted 1
67 (78)
2
18 (21)
$3
1 (1)
Number of defects closed 0
7 (8)
1
65 (76)
2
13 (15)
$3
1 (1)
OR
95% CI
Age, yrs
1.0
0.97–1.04
Multivariate p Value
OR
95% CI
0.77
1.03
0.97–1.09
Male
0.93
0.34–2.53
0.89
1.06
0.23–4.87
0.96
Diabetes
1.58
0.58–4.30
0.37
1.74
0.37–8.20
0.48
Bioprosthetic valve
0.54
0.21–1.37
0.19
0.30
0.05–1.76
0.18
TAVR
1.71
0.45–6.44
0.43
2.51
0.28–22.9
0.27
History of IE
7.83
0.004
15.2
2.2–104.5
0.006
Anterior leak
1.48
0.18
1.94
0.34–11.1
0.46
1.95–21.52 0.84–2.59
Urgent procedure
1.77
0.41–7.67
0.45
2.77
0.39–19.7
0.31
Transthoracic echocardiography
0.55
0.28–1.32
0.18
0.41
0.11–1.59
0.20
AVPII
1.13
0.43–2.94
0.80
1.16
0.24–5.59
0.85
More than 1 defect
3.66
1.36–9.83
0.01
4.01
0.90–17.9
0.069
LVEDD >60 mm
1.12
0.42–3.00
0.82
0.66
0.13–3.34
30 (35)
Apical rail
1 (1.2)
Successful procedure (device placed or not)
94 (90)
Number of devices placed
AVPII ¼ Amplatzer Vascular Plug II; CI ¼ confidence interval; IE ¼ infective endocarditis; LVEDD ¼ left ventricular end-diastolic dimension; OR ¼ odds ratio; TAVR ¼ transcatheter aortic valve replacement.
experience, an arterioapical rail was used in only 1 of 86 cases of aortic PVL closure.
1
55 (70)
2
15 (19)
$3
9 (11)
Important technical considerations
should
be
taken into account to maximize the efficiency and minimize the risks of the procedure.
Device types (AVPII vs. others) AVPII
61 (71)
First, device and sheath compatibility and fit
Other
16 (19)
are crucial to procedural execution. Knowledge of
AVPII plus others
2 (2)
sheath-sizing requirements for each device with and
Residual shunt
without an anchor wire shortens the duration and
None or trivial
22 (26)
Mild
31 (36)
Mild to moderate
17 (20)
Moderate or more
16 (19)
reduces the cost of the procedure. Compatibility charts are provided in Online Figure 1. Second, a feared complication of aortic PVL closure is the impingement of a mechanical or bioprosthetic
53 (62)
Procedural time (min)
86 46
valve leaflet during device deployment. Mechanical
Fluoroscopy time (min)
38 24
leaflet impingement is usually readily recognized with
Contrast load (ml)
46 58
fluoroscopy. However, impingement of bioprosthetic
Length of stay (days)
3.0 5.9
#48-h length of stay
leaflets, albeit rare, is more difficult to recognize but
69 (80)
can be suspected when there is echocardiographic evidence of sudden valvular regurgitation or an
Values are n (%) or mean SD.
increased transvalvular gradient. Detailed assessment
AVPI ¼ Amplatzer Vascular Plug II.
of valve leaflet motion should be performed in every case before releasing the closure device. In rare used in patients with bioprosthetic valves. Although
occasions, device interference with the prosthetic
we have used this technique successfully in patients
valve leaflets can occur after plug release because of
with mechanical prosthesis, we recommend against its
tilting of the device, which would require device
routine use with mechanical valves. A wire across the
removal with a snare or a long, flexible bioptome.
mechanical valve can lead to stuck leaflets with severe
Third, para-aortic leak closure may lead to coro-
aortic regurgitation and result in rapid hemodynamic
nary artery obstruction. Aortography or selective
compromise. If the patient has a mechanical valve and
coronary angiography may be needed to assess ostial
the device could not be delivered without a rail, the left
clearance before device release. Meticulous cardiac
ventricular wire can be snared through a transseptal or
computed tomographic measurement and analyses
transapical puncture, creating an arteriovenous rail
can identify low takeoff of the left or right coronary
and
ostia before the procedure.
an
arterioapical
rail,
respectively.
In
0.62
*Defined as more than mild residual leak at the end of the procedure.
Double or anchor wire
Mild or less
p Value
0.35
our
2422
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 4 Change in New York Heart Association Functional Class at 30 Days After
Aortic Paravalvular Leak Closure
greater than mild). The probability of death or repeat surgery according to residual PVL groups was graphically displayed according to the method of Kaplan and Meier, with comparison of cumulative survival across strata by the log-rank test. Binary logistic regression analysis was used to identify variables independently associated with the failure to reduce the PVL to less than mild (technical failure). Variables included in the model were age, sex, diabetes, prosthesis type (bioprosthesis vs. mechanical, transcatheter heart valve), history of infective endocarditis (IE), location of the PVL, procedure status (elective vs. urgent), imaging guidance (transthoracic vs. transesophageal echocardiography), and device type (AVPII vs. others). All analyses were performed with SPSS version 22 (IBM, Armonk, New York). Statistical significance was inferred at p #0.05.
RESULTS STUDY COHORT. Eighty-six aortic PVL closure pro-
cedures were performed in 80 patients. Baseline characteristics of the study population are shown in Table 1. The mean age was 67.8 14.6 years, 70% were men, and 63% had bioprosthetic valves. The mean number of prior sternotomies was 1.4 0.9 (range 0 to 6). The indication for aortic valve replacement was calcific aortic stenosis in 64%, IE in 9%, aortic regurgitation in 6%, and rheumatic aortic valve disease in 5%. The primary indication for percutaneous PVL (A) New York Heart Association (NYHA) functional class change overall and according to
closure was symptoms of heart failure in 66 patients
the residual leak. (B) Distribution of NYHA functional class before and after paravalvular
(83%), hemolysis in 4 patients (5%), and both in 10
leak closure.
patients (12%). Eight procedures (9.4%) were done urgently in patients not in stable condition who presented with decompensated heart failure soon after STUDY ENDPOINTS. The primary efficacy endpoints
aortic valve replacement. The mean times from valve
of the study were the change in NYHA functional class
implantation to first detection of aortic PVL and to
at 30 days and the elimination of transfusion
percutaneous repair were 22 40 months and 35 46
requirement
hemolysis
months, respectively. Using the Society of Thoracic
requiring blood transfusion. The primary safety
Surgeons risk calculator, the estimated operative
endpoint of the study was the occurrence of acute and
mortality for open repair in the cohort was 5.7 4.6.
in
patients
with
severe
30-day major adverse cardiovascular events, defined as stroke, major vascular complications, tamponade, acute coronary syndrome, or death. Secondary endpoints were: 1) long-term survival from death within the duration of the study; and 2) long-term event-free freedom from repeat cardiac surgery. DATA
ANALYSIS. Continuous
ACUTE PROCEDURAL OUTCOMES. Echocardiographic
guidance was used in all cases. Baseline echocardiographic data are summarized in Table 2. Percutaneous repair was attempted in a total of 105 PVLs in 80 patients. Successful crossing and device deployment were achieved in 94 defects using 114 closure
parameters of the
devices (90%). The AVPII device was used in the ma-
study groups were compared using the Student t test.
jority of cases (88%). The reasons for failure to close the
For comparison of categorical data, we used the
11 remaining leaks were inability to cross the defect
chi-square or Fisher exact test. To examine the impact
with a wire or with a sheath in 8 defects, impingement
of residual regurgitation on outcomes, patients were
of prosthetic leaflet in 1, proximity to a coronary artery
grouped according to the residual PVL (mild or less,
ostium in 1, and coronary dissection in 1.
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
Technical success (defined as mild or less residual PVL) was achieved in 53 patients (62%). The residual
T A B L E 5 Short-Term (30 Days) and Long-Term Clinical
Outcomes of Patients Who Underwent Percutaneous Aortic
PVLs were mild to moderate in 17 patients (20%)
Paravalvular Leak Closure (N ¼ 80)
and
In-hospital outcomes
moderate
or
more
in
16
patients
(18%)
(Table 3). Among multiple baseline and procedural
MACE
6 (7.6)
characteristics, only history of IE predicted more than
Death
2 (2.5)
mild residual PVL after the procedure (Table 4).
Procedure-related death
1 (1.3)
In-hospital major
adverse
cardiovascular
events
occurred in 6 patients (7.6%). These included death in 2 (2.5%) (1 due to tamponade and hemothorax after an apical puncture and 1 due to persistent cardiogenic
30-day outcomes MACE
10 (12.5)
Death
5 (6.3)
Mean change in NYHA functional class
0.94 0.72
NYHA functional class
shock in a patient who underwent successful salvage
I
19 (27.0)
PVL closure immediately after surgical aortic valve
II
32 (46.0)
replacement), stroke in 1 (1.2%), retroperitoneal
III
16 (23.0)
bleeding in 1 (1.2%), tamponade in 1 (1.2%), and cor-
IV
3 (4.0)
onary dissection in 1 (1.2%). The mean length of
Died or missing
10
hospital stay was 2.3 3.2 days for patients who un-
Elimination of transfusion requirements
7 (88.0)
derwent elective PVL closure compared with 10.8 15.7
days
for
patients
who
underwent
urgent
procedures (p < 0.001). SHORT-TERM (30-DAY) OUTCOMES. C l i n i c a l e f fi c a c y .
Clinical follow-up (NYHA functional class assessment) at 30 days was available in 70 patients (93%).
Long-term outcomes Mean follow-up (months)
27 25
Death
22 (27.5)
Redo valve replacement
10 (13.0)
Repeat percutaneous closure
5 (6.3)
CHF readmission
18 (23.0)
Stroke
5 (6.0)
NYHA functional class at maximum follow up
The primary endpoint of the study was achieved in
I
19 (24.0)
51 patients (64%). The mean change in NYHA func-
II
24 (30.0)
tional class was 0.9 0.5 (Figure 4). Patients who
III
18 (23.0)
had successful reductions in PVL grade to mild or less experienced significantly more improvement in NYHA functional class (mean change 1.21, from 2.93
Values are n (%) or mean SD. CHF ¼ congestive heart failure; MACE ¼ major adverse cardiovascular event(s); NYHA ¼ New York Heart Association.
0.62 to 1.72 0.73) compared with those with more than mild residual leak (mean change 0.51, from 3.03 0.57 to 2.52 0.74) (p < 0.001) (Figure 4). In patients with severe hemolysis requiring blood
follow-up, all-cause mortality was 27.5%, and redo
transfusion (n ¼ 8), transfusion requirement was
valve replacement for residual or recurrent PVL was
eliminated in 7 cases (88%).
13% (Table 5). Compared with patients who had more
o u t c o m e s . Among the 78 patients dis-
than mild post-procedure leak, those who had mild or
charged from the hospital, 5 major adverse cardio-
less residual leak had better freedom from repeat
vascular events occurred in 4 patients (5.1%): 3 deaths
cardiac surgery but long-term survival rates were
Safety
and 2 hemorrhagic strokes. Two deaths occurred after
similar (Figure 5). In patients who achieved event-free
successful PVL closure; 1 was at day 6 because of a
survival, the initial improvement in NYHA functional
hemorrhagic stroke, and 1 was at day 27 because of an
class persisted at maximum follow-up (mean NYHA
unknown cause in a 35 year-old patient with a 27-mm
functional class 1.95 0.78). The magnitude of
Starr-Edwards Silastic Ball valve. One death occurred
NYHA functional class improvement was more sig-
at day 28 because of decompensated heart failure
nificant in patients with mild or less residual leak
after an unsuccessful attempt for PVL closure in an
(mean NYHA functional class 1.76 0.74 vs. 2.24
86-year-old patient with a 23-mm SAPIEN-XT valve.
0.76; p ¼ 0.027).
Both hemorrhagic strokes occurred between 2 and 5 days after the procedure in patients who were bridged to therapeutic warfarin with low–molecular weight heparin.
DISCUSSION The principal findings of the present investigation are
LONG-TERM OUTCOMES. Median follow-up for the
as follows. 1) Percutaneous repair of aortic PVL can
study patients was 18.5 months, with a range of
be performed safely with a low incidence of major
1 to 101 months (mean 27 25 months). During
complications. 2) Cannulation and closure device
2423
2424
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
F I G U R E 5 Kaplan-Meier Curves Showing Survival Free of Death and
Repeat Cardiac Surgery According to Degree of Residual Paravalvular Leak
PVL is seen predominantly in patients with moderate and severe PVL (17,18). We classified successful PVL closure on the basis of the residual leak to mild or less (technical success) and more than mild (technical failure). Similar to what has been observed in the post-TAVR PVL literature, our findings suggest that more
than
mild
residual
PVL
after
percutan-
eous closure is associated with less symptomatic improvement and a lower rate of event-free survival. Although there was no difference in all-cause mortality between the 2 groups, our study is underpowered to detect mortality differences given the small sample size. Achieving complete or near complete obliteration of aortic PVL, however, can be challenging. As illustrated in this study, although successful crossing of aortic PVL and deployment of closure device(s) across the leaks were achieved in 90% of defects, reduction in PVL to mild or less was possible in only 62% of patients. This can be due to a number of reasons. First, a significant predictor of more than mild residual PVL in this study was a history of IE. The process of inflammation and healing in IE can lead to scar formation and/or fibrosis and may result in tissue fragility, which can make complete abolition of the leak more challenging. Other predictors of technical failure are the presence of mechanical prostheses,
transcatheter
heart
valve,
and
urgent
indications for PVL closure. Bioprosthetic valves generally have lower risk for device-leaflet interaction. In contrast, the spatial relationship of mechanical prosthesis occluder discs relative to the defect(s) is a key determinant of the size and number of devices that can be implanted without leaflet impingement. Therefore, technical success rates are expected to be lower with mechanical prostheses (11). Patients who develop significant PVL after PVL ¼ paravalvular leak.
TAVR represent another challenging group. In these patients, if the transcatheter heart valve is properly positioned and adequately expanded, the PVL is due
deployment across aortic PVL was achieved in the
to the lack of surgical excision of the old calcified
vast majority of PVLs (90%). However, successful
valve, resulting in multiple defects of small dimen-
reduction of the PVL to mild or less was only achieved
sions (19). Smaller profile devices such as the
in 62% of patients. 3) History of IE was strongly
Amplatzer Vascular Plug IV have been used in these
correlated with significant residual leak after percu-
patients, but the technical success rate has been
taneous PVL closure. 4) Successful PVL reduction to
only modest (20–22).
mild or less resulted in quick and durable symptom-
Second, despite the growing prevalence of PVL,
atic relief and reduced the need for redo cardiac
there are no devices that were designed, tested, or
surgery.
approved for PVL closure (23). The AVPII is the most
There is growing evidence from the global experi-
commonly used off-label device because of its sta-
ence with transcatheter aortic valve replacement
bility and low profile. However, many patients
(TAVR) that PVL after TAVR is associated with poor
have crescentic or irregular shaped PVLs, and the
long-term outcomes. However, the negative impact of
AVPII may not be adequate for treatment of such
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
defects (24). In recent years, the Amplatzer Vascular
Third, residual PVL grade in our study was corre-
Plug III has been increasingly used for PVL closure
lated with symptomatic improvement and need for
given its oblong shape (25,26). Also, a new purpose-
redo surgery. However, grading of aortic PVL can be
specific device, the Occlutech PLD occluder (Occlu-
quite challenging. Echocardiographic measures used
tech, Jena, Germany), was designed to tackle a large
to grade PVL are semiquantitative and suffer from
range of PVL sizes and morphologies (26). Early
limited validation. This could lead to interpretation
experience with the Occlutech PLD device showed
variability, which may affect the results of this study.
results (26,27). Unfortunately,
Fourth, follow-up laboratory data on patients with
neither the Amplatzer Vascular Plug III nor the
hemolysis were limited because of the referral nature
Occlutech is available in the United States. Another
of our center. However, in those with severe hemo-
consideration to increase the success rate of the
lysis requiring blood transfusion, PVL closure elimi-
procedure is the possible use of transapical access in
nated blood transfusion in all but 1 patient.
very encouraging
selected cases. Transapical access has been used pri-
Last, the small number of patients enrolled in this
marily in the treatment of mitral PVL for medial and
study may affect the reliability of the data, and the
anterior leaks or when concomitant aortic and mitral
validity of certain statistical analyses (e.g., logistical
PVL closure is planned (12). Although transapical ac-
regressions). However, to our knowledge this is the
cess is potentially associated with higher complica-
largest reported series of percutaneous aortic PVL
tion rates, these can be minimized by careful access
closure. The descriptive data in our study are very
planning with a pre-acquired computed tomographic
valuable in closing the knowledge gap on the
angiogram and closure of the access site with vascular
management of this complex entity.
plugs or occluders (12). Despite the low rate of adverse events in our series, further modification of the current technique
CONCLUSIONS
may further lower the risk for these complications.
Percutaneous aortic PVL closure can be performed
First, we observed 2 hemorrhagic strokes in patients
with high technical success and low complication
with atrial fibrillation who were bridged with low–
rates. Successful PVL reduction to mild or less results
molecular weight heparin. Recently, the BRIDGE
in quick and durable symptomatic relief and reduces
(Bridging Anticoagulation in Patients Who Require
the need for redo cardiac surgery. Attempts should be
Temporary Interruption of Warfarin Therapy for an
made to accomplish adequate reduction in PVL to
Elective Invasive Procedure or Surgery) trial sug-
optimize clinical outcomes.
gested no benefit and higher bleeding events in patients who underwent periprocedural bridging
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
with low–molecular weight heparin for atrial fibril-
Charanjit S. Rihal, Mayo Clinic College of Medicine,
lation (28). Therefore, we believe that bridging
Division of Cardiovascular Diseases, 200 First Street
anticoagulation should be avoided when possible.
SW, Rochester, Minnesota 55905. E-mail: rihal@
Second, a meticulous post-procedural protocol that
mayo.edu.
includes frequent echocardiographic examinations should be implemented when an apical puncture is
PERSPECTIVES
performed to aid in early detection and management of hemothorax or tamponade. Closing the apical puncture site with a vascular plug should also be considered when sheath sizes >4 F are used. STUDY LIMITATIONS. First, the retrospective nature
of this study has known limitations, including potential for referral basis. Notably, serial echocardiography was not performed, and data on residual regurgitation at final follow-up were not available, because of the referral nature of our clinical practice. Second, the practice of PVL closure might differ outside the United States because of the availability of purpose-specific devices. Therefore, the results of this study may not be generalizable to practices outside the United States.
WHAT IS KNOWN? Percutaneous closure has emerged as an alternative therapy to repeat valve surgery for patients with symptomatic aortic PVL. However, procedural and long-term outcomes of percutaneous closure techniques are not known. WHAT IS NEW? Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to grade mild or less, which was achieved in two-thirds of the patients. WHAT IS NEXT? Further studies are needed to assess the effectiveness of PVL closure with purpose-specific devices.
2425
2426
Alkhouli et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 23, 2016 DECEMBER 12, 2016:2416–26
Percutaneous Aortic Paravalvular Leak Closure
REFERENCES 1. Miller DL, Morris JJ, Schaff HV, Mullany CJ, Nishimura RA, Orszulak TA. Reoperation for aortic valve periprosthetic leakage: identification of patients at risk and results of operation. J Heart Valve Dis 1995;4:160–5. 2. Hwang HY, Choi JW, Kim HK, Kim KH, Kim KB, Ahn H. Paravalvular leak after mitral valve replacement: 20-year follow-up. Ann Thorac Surg 2015;100:1347–52. 3. Davila-Roman VG, Waggoner AD, Kennard ED, et al. Prevalence and severity of paravalvular regurgitation in the Artificial Valve Endocarditis Reduction Trial (AVERT) echocardiography study. J Am Coll Cardiol 2004;44:1467–72.
closure of periprosthetic paravalvular leaks. J Am Coll Cardiol 2011;58:2210–7. 13. Cho IJ, Moon J, Shim CY, et al. Different clinical outcome of paravalvular leakage after aortic or mitral valve replacement. Am J Cardiol 2011;107: 280–4. 14. Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of prosthetic valves with echocardiography and Doppler ultrasound: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging
4. Akins CW, Bitondo JM, Hilgenberg AD, Vlahakes GJ, Madsen JC, MacGillivray TE. Early and late results of the surgical correction of cardiac prosthetic paravalvular leaks. J Heart Valve Dis 2005;14:792–9.
Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, endorsed by the
5. Taramasso M, Maisano F, Denti P, et al. Surgical treatment of paravalvular leak: Long-term results in a single-center experience (up to 14 years). J Thorac Cardiovasc Surg 2015;149:1270–5.
American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography. J Am Soc Echocardiogr
6. Genoni M, Franzen D, Vogt P, et al. Paravalvular leakage after mitral valve replacement: improved long-term survival with aggressive surgery? Eur J Cardiothorac Surg 2000;17:14–9. 7. Orszulak TA, Schaff HV, Danielson GK, Pluth JR, Puga FJ, Piehler JM. Results of reoperation for periprosthetic leakage. Ann Thorac Surg 1983;35: 584–9. 8. Millan X, Skaf S, Joseph L, et al. Transcatheter reduction of paravalvular leaks: a systematic review and meta-analysis. Can J Cardiol 2015;31: 260–9. 9. Smolka G, Pysz P, Jasinski M, et al. Multiplug paravalvular leak closure using Amplatzer Vascular Plugs III: a prospective registry. Catheter Cardiovasc Interv 2016;87:478–87. 10. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Long-term follow-up of percutaneous repair of paravalvular prosthetic regurgitation. J Am Coll Cardiol 2011;58:2218–24. 11. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Percutaneous repair of paravalvular prosthetic regurgitation: acute and 30-day outcomes in 115 patients. Circ Cardiovasc Interv 2011;4:314–21. 12. Ruiz CE, Jelnin V, Kronzon I, et al. Clinical outcomes in patients undergoing percutaneous
2009;22:975–1014. 15. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease: technic, indications and interpretations in 700 cases. Am J Cardiol 1964; 14:437–47. 16. National Center for Health Statistics. National Death Index User’s Guide. Available at: https:// www.cdc.gov/nchs/data/ndi/ndi_users_guide.pdf. Accessed September 8, 2016. 17. Jerez-Valero M, Urena M, Webb JG, et al. Clinical impact of aortic regurgitation after transcatheter aortic valve replacement: insights into the degree and acuteness of presentation. J Am Coll Cardiol Intv 2014;7:1022–32. 18. Athappan G, Patvardhan E, Tuzcu EM, et al. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: meta-analysis and systematic review of literature. J Am Coll Cardiol 2013;61:1585–95. 19. Eleid MF, Cabalka AK, Malouf JF, Sanon S, Hagler DJ, Rihal CS. Techniques and outcomes for the treatment of paravalvular leak. Circ Cardiovasc Interv 2015;8:e001945.
20. Gafoor S, Franke J, Piayda K, et al. Paravalvular leak closure after transcatheter aortic valve replacement with a self-expanding prosthesis. Catheter Cardiovasc Interv 2014;84: 147–54. 21. Feldman T, Salinger MH, Levisay JP, Smart S. Low profile vascular plugs for paravalvular leaks after TAVR. Catheter Cardiovasc Interv 2014;83: 280–8. 22. Okuyama K, Jilaihawi H, Kashif M, et al. Percutaneous paravalvular leak closure for balloon-expandable transcatheter aortic valve replacement: a comparison with surgical aortic valve replacement paravalvular leak closure. J Invasive Cardiol 2015;27:284–90. 23. Kim MS, Casserly IP, Garcia JA, Klein AJ, Salcedo EE, Carroll JD. Percutaneous transcatheter closure of prosthetic mitral paravalvular leaks: are we there yet? J Am Coll Cardiol Intv 2009;2:81–90. 24. McElhinney DB. Will there ever be a Food and Drug Administration–approved device for transcatheter paravalvular leak closure? Circ Cardiovasc Interv 2014;7:2–5. 25. Cruz-Gonzalez I, Rama-Merchan JC, ArribasJimenez A, et al. Paravalvular leak closure with the Amplatzer Vascular Plug III device: immediate and short-term results. Rev Esp Cardiol (Engl Ed) 2014;67:608–14. 26. Bedair R, Morgan GJ, Bapat V, et al. Early experience with the Occlutech PLD occluder for mitral paravalvar leak closure through a hybrid transapical approach. EuroIntervention 2015;11. 20150419–01. 27. Yildirim A, Goktekin O, Gorgulu S, et al. A new specific device in transcatheter prosthetic paravalvular leak closure: a prospective two-center trial. Catheter Cardiovasc Interv 2016; 88:618–24. 28. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373: 823–33.
KEY WORDS aortic regurgitation, paravalvular leak, percutaneous repair A PPE NDI X For a supplemental figure, please see the online version of this article.