Introduction
Rapid-deployment aortic valves (RDAVs) are known for ease of implantation, as only
a few sutures are required to secure the device efficiently compared with conventional
sutured bioprosthesis.[1] In cardiac surgery, prolonged cardiopulmonary bypass (CPB) time and aortic cross-clamp
time are strong independent risk factors for postoperative mortality and morbidity,
particularly in older patients with serious comorbidities.[2]
[3] Rapid-deployment aortic valve replacement (RDAVR) procedures have demonstrated a
significant reduction in the operation time by minimizing CPB and aortic cross-clamp
durations achieved by eliminating the passage and tying of sutures, resulting in fewer
complications and improved outcomes in low and high-risk patients.[4]
[5]
[6] Moreover, several studies have indicated that isolated RDAVR enhances hemodynamic
profile, reduces myocardial ischemia, decreases patient–prosthesis mismatch, and facilitates
other minimally invasive approaches compared with conventional bioprosthesis implantation.[6]
[7]
[8]
[9]
[10]
[11]
Aortic stenosis (AS) is highly prevalent among patients with coronary artery disease
(CAD). In such patients, surgical interventions often involve aortic valve replacement
(AVR) combined with coronary artery bypass graft (CABG) procedures to treat both conditions.[12]
[13] Given the encouraging outcomes and hemodynamic benefits associated with RDAVR, the
integration of RDAVR with CABG would be advantageous in managing severe AS and significant
CAD.[10]
[13] Gonzalez-Barbeito et al reported an appreciable midterm outcome for combined RDAVR
using the Edwards INTUITY valve system with other cardiac procedures and supported
the utility of RDAVR in concomitant surgeries including CABG where surgical time is
expected to prolong.[5]
To our knowledge, robust evidence-based data on the efficiency and performance of
RDAVR combined with CABG are scarce. Consequently, follow-up studies and registry
data are necessary to adequately assess the safety, durability, and long-term outcomes
of this combined approach. Therefore, in this study, we present the 3-year findings
from the prospective INCA German registry, explicitly focusing on the clinical outcomes
of combined RDAVR with CABG procedures.
Method/Design
INCA is a prospective, non-randomized multicenter registry that included data from
the patients who underwent RDAVR with concomitant CABG across 10 high-volume cardiac
institutions in Germany between 2017 and January 2020.
Patient Population
The study included consecutive patients (≥18 years of age) with aortic valve disease
and CAD indicated for a combined RDAVR using Edwards INTUITY Elite aortic valve and
CABG willing to provide informed consent before enrollment.
The study excluded patients with emergency indications for surgery, required reoperation,
have other cardiac diseases requiring additional cardiac surgery, have acute endocarditis
or other systemic infections, and required mechanical prosthesis. Additionally, patients
with anatomical contraindications to the Edwards INTUITY Elite valve system were excluded
from the study.
Data Documentation
Baseline clinical parameters, as well as patient-specific data such as established
risk scores (Logistic EuroSCORE I & EuroSCORE II, STS score, and Syntax score I) to
estimate the perioperative risk, were collected and documented during screening. The
local cardiac surgical team at each center evaluated patients according to the inclusion
and exclusion criteria and determined the number of necessary coronary bypasses based
on the morphology and location of the coronary stenoses.
Further, the intraoperative parameters and discharge information were appropriately
collected and documented. Post-surgery follow-up data were collected at 30 days, 1
year, and 3 years through a telephone interview with the patient. Additionally, at
3 years, a follow-up examination at the center was conducted. All patient data were
anonymized and captured using a specifically designed electronic case report form
(eCRF) within a secure, password-protected, web-based electronic database.
Objectives
The primary objective was to determine all-cause mortality after 30 days in patients
undergoing combined RDAVR with CABG. The secondary objective was to assess the hemodynamic
performance of the Edwards INTUITY Elite bioprosthesis and further durability parameters,
early (≤30 days) and late (>30 days to 3 years) clinical outcomes, and quality of
life (QoL). Clinical outcomes of interest were all-cause, cardiovascular, and valve-related
mortality, structural valve deterioration (SVD) according to VARC-2 criteria, reoperation
related to valve or CABG or bleeding/tamponade, permanent pacemaker implantation (PPI),
unplanned percutaneous coronary intervention (PCI), myocardial infarction (MI), and
bypass obstruction. In addition, we compared the New York Heart Association (NYHA)
functional class at 3 years post-surgery. QoL was assessed using the Short Form-12
Health Survey Version 2 (SF-12v2) questionnaire.
Statistical Analysis
Data were analyzed using descriptive statistics, with categorical variables presented
as absolute values and frequencies (%) and the continuous variables presented as means
(standard deviation [SD]) and median (interquartile range [IQR]). Test for normal
distribution was performed using Kolmogorov-Smirnov test. Wilcoxon signed ranks test
for paired data was used to compare QoL scores between baseline and follow-up visits.
A p-value of <0.05 was considered statistically significant. Statistical analysis was
performed using SPSS Version 28.0 (Armonk, NY, IBM Corp.).[14]
Results
A total of 224 patients undergoing RDAVR with concomitant CABG receiving Edwards INTUITY
Elite aortic valve meeting the inclusion criteria were included in the present analysis.
Patient Characteristics
Patients had a mean age of 73.6 ± 6.1 years, primarily males (80.4%), had a BMI of
28.3 ± 4.1 kg/m2, and mean systolic blood pressure of 138.4 ± 19.0 mm Hg and diastolic blood pressure
of 75.0 ± 9.7 mm Hg ([Table 1]). The mean logistic EuroSCORE I and EuroSCORE II of the patients were 7.8 ± 6.0
and 3.5 ± 2.9%, respectively, with an STS Risk Score of 3.8 ± 3.8 and Syntax score
I of 13.0 ± 8.6. Furthermore, 139 patients (62.1%) had NYHA class III/IV symptoms,
and 45 patients (26.9%) had angina Canadian Cardiovascular Society (CCS) III/IV symptoms.
Common comorbidities included arterial hypertension, CAD with left anterior descending
artery abnormality, myocardial infarction, type II diabetes, and peripheral vascular
disease. Moreover, 57 patients (25.4%) had a history of previous PCI, and 11 patients
(4.9%) had a history of previous permanent pacemakers.
Table 1
Patient characteristics
|
Mean ± SD or n (%)
N = 224
|
|
Age (years)
|
73.6 ± 6.1
|
|
Female gender
|
44 (19.6)
|
|
Height (cm)
|
171.3 ± 8.7
|
|
Weight (kg)
|
83.2 ± 14.3
|
|
Body mass index (k/m2)
|
28.3 ± 4.1
|
|
Systolic blood pressure (mmHg)
|
138.4 ± 19.0
|
|
Diastolic blood pressure (mmHg)
|
75.0 ± 9.7
|
|
Heart rate (bpm)
|
73.4 ± 11.5
|
|
NYHA class III or IV
|
139 (62.1)
|
|
Angina CCS class 3 or 4
|
45 (26.9)
|
|
Logistic EuroSCORE I
|
7.8 ± 6.0
|
|
EuroSCORE II (%)
|
3.5 ± 2.9
|
|
STS Risk Score
|
3.8 ± 3.8
|
|
Syntax Score I
|
13.0 ± 8.6
|
|
Medical history
|
|
|
Coronary artery disease
|
|
|
RCA affected
|
161 (71.9)
|
|
LCA/LM affected
|
45 (20.1)
|
|
LAD affected
|
183 (81.7)
|
|
LCX affected
|
121 (54.0)
|
|
Recent myocardial infarction
|
44 (19.6)
|
|
Previous percutaneous interventions
|
57 (25.4)
|
|
Permanent pacemaker
|
11 (4.9)
|
|
Diabetes Type I
|
3 (1.3)
|
|
Diabetes Type II
|
81 (36.2)
|
|
Peripheral vascular disease
|
37 (16.5)
|
|
Transient ischemic attack/Stroke
|
20 (8.9)
|
|
Chronic obstructive coronary disease
|
19 (8.5)
|
|
Arterial hypertension
|
175 (78.1)
|
|
Pulmonary hypertension
|
19 (8.5)
|
|
Dialysis
|
3 (1.3)
|
|
Laboratory
|
|
|
Creatinine >2.3 mg/dL
|
4 (1.8)
|
|
Creatinine (mg/dL)
|
1.08 ± 0.48
|
|
Dialysis
|
3 (1.3)
|
|
Lactate dehydrogenase (U/L)
|
212.9 ± 52.6
|
|
S-Bilirubin (mg/dL)
|
0.62 ± 0.35
|
Abbreviations: CCS, Canadian Cardiovascular Society; EuroSCORE, European System for
Cardiac Operative Risk Estimation; IQR, interquartile range, LAD; left anterior descending
artery; LCA, left coronary artery; LCX, left circumflex coronary artery; LM, left
main artery; NYHA, New York Heart Association; RCA, right coronary artery; SD, standard
deviation; STS, Society of Thoracic Surgeon.
Procedural Details
Among the total population (n = 224), 198 patients (88.4%) had tricuspid valve morphology ([Table 2]). The left internal mammary artery (IMA) was used for revascularization in 146 patients
(65.2%), the right IMA in 3 patients (1.3%), and both IMAs were used in 25 patients
(11.2%), and the radial artery was used in only 4 patients (1.8%). The number of distal
arterial anastomoses was one in 134 patients (59.8%), two in 33 patients (14.7%),
three in 7 patients (3.1%), and four in 2 patients (0.9%). The venous graft was performed
in 170 patients (75.9%), with the majority receiving one anastomosis (distal in 96
patients [56.5%] or proximal in 98 patients [57.6%]). However, the mean number of
distal arterial and venous anastomoses was 3.13 ± 1.56.
Table 2
Interventional details
|
Mean ± SD, Median (IQR) or n (%)
N = 224
|
|
Aortic valve morphology
|
|
|
Tricuspid
|
198 (88.4)
|
|
Bicuspid
|
12 (5.4)
|
|
Functional bicuspid
|
14 (6.3)
|
|
Annulus size (Edwards INTUITY sizer) (mm)
|
23.9 ± 2.1
|
|
Annulus diameter (Hegar sizer) (mm)
|
23.5 ± 2.0
|
|
Internal mammary artery
|
|
|
No
|
50 (22.3)
|
|
Left
|
146 (65.2)
|
|
Right
|
3 (1.3)
|
|
Both
|
25 (11.2)
|
|
Radial artery
|
4 (1.8)
|
|
Number of distal arterial anastomoses
|
|
|
0
|
48 (21.4)
|
|
1
|
134 (59.8)
|
|
2
|
33 (14.7)
|
|
3
|
7 (3.1)
|
|
4
|
2 (0.9)
|
|
Venous grafts
|
170 (75.9)
|
|
Number of distal venous anastomoses
|
|
|
0
|
2 (1.2)
|
|
1
|
96 (56.5)
|
|
2
|
57 (33.5)
|
|
3
|
13 (7.6)
|
|
4
|
2 (1.2)
|
|
Number of proximal venous anastomoses
|
|
|
0
|
17 (10.0)
|
|
1
|
98 (57.6)
|
|
2
|
49 (28.8)
|
|
3
|
6 (3.5)
|
|
4
|
0 (0)
|
|
Number of distal arterial and venous anastomoses
|
3.13 ± 1.56
|
|
Intraoperative complications
|
|
|
Aortic rupture/dissection
|
0 (0)
|
|
Annulus rupture
|
0 (0)
|
|
Coronary artery obstruction
|
0 (0)
|
|
Prosthesis dislocation
|
0 (0)
|
|
Off-pump CABG
|
1 (0.4)
|
|
On-pump beating-heart CABG
|
8 (3.6)
|
|
Duration of intervention
|
|
|
Aortic cross-clamp time (min)
|
79.4 ± 24.1
73.5 (IQR 60.8; 95.3)
|
|
Cardiopulmonary bypass time (min)
|
109.6 ± 34.5
104.5 (IQR 83.0; 134.0)
|
|
Operation time (skin-to-skin) (min)
|
224.2 ± 62.7
211 (IQR 178; 261.5)
|
|
Implantation 1st attempt
|
|
|
INTUITY Elite valve size (mm)
|
23.8 ± 2.1
25 (IQR 23; 25)
|
|
19
|
10 (4.5)
|
|
21
|
32 (14.3)
|
|
23
|
69 (30.8)
|
|
25
|
81 (36.2)
|
|
27
|
32 (14.3)
|
|
Paravalvular leak (visually)
|
10 (4.5)
|
|
Extra stitch(es) placed
|
6 (2.7)
|
|
Valve implant time (min)
|
14.1 ± 7.4
12 (IQR 8; 19)
12 (8; 19)
|
|
Attempt successful
|
221 (98.7)
|
|
Implantation 2nd attempt
|
|
|
2nd attempt performed
|
2 (0.9)
|
|
Paravalvular leak (visually)
|
1 (0.4)
|
|
Extra stitch(es) placed
|
0
|
|
Valve implant time (min)
|
12
|
|
Second cross-clamp needed
|
1 (0.4)
|
|
Attempt successful
|
2 (0.9)
|
Abbreviations: CABG, coronary artery bypass graft; IQR, interquartile range; SD, standard
deviation.
Regarding the type of CABG performed, one patient (0.4%) underwent off-pump CABG,
and eight patients (3.6%) had beating-heart CABG, whereas the majority (96%; 215 patients)
underwent on-pump CABG. The mean duration of operation (skin-to-skin) was 224.2 ± 62.7 minutes,
with a mean cross-clamp time of 79.4 ± 24.1 and cardiopulmonary bypass (CBP) time
of 109.6 ± 34.5.
The first valve implantation was successful in 221 patients (98.7%) with a mean valve
implantation time of 14.1 ± 7.4 minutes. The mean valve size utilized was 23.8 ± 2.1 mm,
as most patients (36.2%) received 25-mm size valve. Notably, there were no (0%) intraoperative
complications such as aortic rupture/dissection, annulus rupture, coronary artery
obstruction, or prosthesis dislocation reported in any case. However, a visual paravalvular
leak was noted in only one patient (0.4%).
Hospital Stays and Discharge
The overall mean duration of hospital stay was 12.0 ± 6.7 days, with a mean intensive
care unit (ICU) stay of 3.4 ± 4.8 days and a mean duration of mechanical ventilation
of 17.5 ± 34.3 hours ([Table 3]).
Table 3
Hospital stay and discharge
|
Mean ± SD, Median (IQR) or n (%)
N = 224
|
|
Length of hospital stay (days)
|
12.0 ± 6.7
2 (IQR 1; 4)
|
|
ICU length of stay (days)
|
3.4 ± 4.8
10 (IQR 8;14)
|
|
Duration of mechanical ventilation (h)
|
17.5 ± 34.3
|
|
Discharged to
|
|
|
Home
|
50 (22.3)
|
|
Standard rehabilitation
|
109 (48.7)
|
|
Other hospital
|
60 (26.8)
|
|
Death
|
5 (2.2)
|
|
Complications after surgery
|
|
|
Transient ischemic attack/stroke
|
6 (2.7)
|
|
INTUITY Elite related
|
0 (0)
|
|
Delirium
|
31 (13.8)
|
|
Reoperations due to:
|
|
|
Bleeding/tamponade
|
17 (7.6)
|
|
Other than bleeding
|
2 (0.9)
|
|
INTUITY Elite valve
|
1 (0.4)
|
|
CABG
|
1 (0.4)
|
|
Platelet concentrates used
|
60 (26.8)
|
|
Deep sternal wound infection
|
4 (1.8)
|
|
Unplanned PCI
|
0 (0)
|
|
Myocardial infarction
|
1 (0.4)
|
|
MI related to INTUITY Elite valve
|
0 (0)
|
|
New PPI
|
17 (7.6)
|
|
PPI valve-related
|
12 (5.4)
|
|
Vascular complication
|
2 (0.9)
|
|
Peripheral obstruction
|
2 (0.9)
|
|
Aortic dissection
|
0 (0)
|
|
Related to INTUITY Elite valve
|
0 (0)
|
|
Laboratory parameters
|
|
|
Dialysis (new onset post AVR)
|
5 (2.2)
|
|
Creatinine
|
1.12 ± 0.49
|
|
Creatinine >2.3 mg/dL
|
6 (2.7)
|
|
Glomerular filtration rate
|
|
|
> 85
|
65 (29.0)
|
|
50–85
|
117 (52.2)
|
|
< 50
|
42 (18.8)
|
|
Lactate dehydrogenase (U/L)
|
328.2 ± 136.1
|
|
S-Bilirubin
|
0.74 ± 0.51
|
|
Haptoglobin
|
64.1 ± 74.5
|
Abbreviations: AVR, aortic valve replacement; CABG, coronary artery bypass graft;
ICU, intensive care unit; IQR, interquartile range; MI, myocardial infarction; PCI,
percutaneous coronary intervention; PPI, permanent pacemaker implantation; SD, standard
deviation.
After the procedure, most patients were discharged to the standard cardiac rehabilitation
unit (48.7%), followed by other hospitals (26.8%) and home (22.3%). Among all patients,
five patients (2.2%) died after surgery due to electromechanical decoupling (n = 1), ventricular fibrillation (n = 1), multi-organ failure (n = 2), and myocardial infarction (n = 1).
Post-surgery, 31 patients (13.8%) experienced delirium, and 6 patients (2.7%) had
a cerebrovascular accident/stroke, which was unrelated to the Edwards INTUITY Elite
aortic valve. Notably, 17 patients (7.6%) required reoperation due to bleeding or
tamponade, 1 patient (0.4%) reoperated due to INTUITY Elite valve issue (0.4%), and
1 patient (0.4%) reoperated due to CABG. Furthermore, four patients (1.8%) had post-surgical
deep sternal wound infection, two patients (0.9%) had vascular complications due to
peripheral obstruction, and one patient (0.4%) had MI unrelated to valve implantation.
Notably, 17 patients (7.6%) required new PPI in which 12 patients (5.4%) required
pacemakers due to valve implantation. Five patients (2.2%) required post-AVR dialysis
(new onset).
ECG and Echocardiography Up to 3 Years
After the procedure, atrial fibrillation (AF) was noted in 32 patients (14.5%) upon
discharge (19 patients had a new onset of AF), 9 patients (10.8%) exhibited AF at
1 year, and 12 patients (9.3%) at 3-year follow-up ([Table 4]). Echocardiography revealed a consistent decrease in mean aortic valve pressure
gradient (AV PG) at discharge (9.2 ± 3.7 mmHg), at 1 year (8.6 ± 3.1 mmHg), and 3
years (8.9 ± 4.6 mmHg) post-surgery compared with baseline (39.4 ± 13.4 mmHg). Conversely,
the mean effective orifice area (EOA; 0.81 ± 0.23 cm2) increased after surgery, measuring 1.90 ± 0.55 cm2 at discharge, 2.1 ± 0.5 cm2 at 1 year, and 2.0 ± 0.5 cm2 at 3-year follow-up, compared with baseline EOA (0.81 ± 0.23 cm2). In addition, the mean pulmonary arterial pressure-systolic (PAP sys) was decreased
from 34.2 ± 11.6 mmHg (baseline) to 25.7 ± 10.2 mmHg at 1 year and 27.7 ± 8.5 mmHg
at 3 years follow-up.
Table 4
Electrocardiography and echocardiography baseline up to 3 years
|
Mean ± SD or n (%)
|
Baseline
|
Discharge
|
1 year
|
3 years
|
|
Electrocardiogram
|
|
|
|
|
|
Paced
|
6 (2.7)
|
23 (10.4)
|
11 (13.3)
|
16 (12.4)
|
|
Sinus rhythm
|
189 (85.5)
|
175 (79.2)
|
63 (75.9)
|
110 (85.3)
|
|
Atrial fibrillation
|
26
|
32 (14.5)
|
9 (10.8)
|
12 (9.3)
|
|
Atrial fibrillation (new onset)
|
|
19 (8.6)
|
|
|
|
Atrial flutter
|
0 (0)
|
2 (0.9)
|
0
|
0
|
|
Atrioventricular block
|
|
|
|
|
|
1st degree
|
16 (7.2)
|
26 (11.8)
|
7 (8.4)
|
17 (13.2)
|
|
2nd degree
|
3 (1.4)
|
1 (0.5)
|
0
|
0
|
|
3rd degree
|
0 (0)
|
5 (2.3)
|
3 (3.6)
|
3 (2.3)
|
|
LBBB complete
|
5 (2.3)
|
43 (19.7)
|
16 (19.5)
|
21 (16.4)
|
|
RBBB complete
|
3 (1.4)
|
2 (0.9)
|
1 (1.2)
|
4 (3.1)
|
|
Ventricular tachycardia
|
0
|
2 (0.9)
|
0
|
2 (1.6)
|
|
Unknown
|
1 (0.5)
|
1 (0.5)
|
0
|
0
|
|
Echocardiography
|
|
|
|
|
|
Peak AV PG (mmHg)
|
64.9 ± 20.8
|
17.3 ± 6.6
|
15.6 ± 5.8
|
15.6 ± 6.7
|
|
Mean AV PG (mmHg)
|
39.4 ± 13.4
|
9.2 ± 3.7
|
8.6 ± 3.1
|
8.9 ± 4.6
|
|
LVOT VTI (cm)
|
20.8 ± 9.3
|
19.1 ± 8.2
|
24.7 ± 14.8
|
20.7 ± 5.4
|
|
LVOT Diameter (mm)
|
21.2 ± 7.4
|
–
|
17.0 ± 14.5
|
21.9 ± 6.3
|
|
LVEDD (mm)
|
52.5 ± 36.2
|
47.7 ± 7.3
|
49.1 ± 5.4
|
48.9 ± 5.7
|
|
EOA (cm2)
|
0.81 ± 0.23
|
1.90 ± 0.55
|
2.1 ± 0.5
|
2.0 ± 0.5
|
|
EOA indexed (cm2/m2)
|
0.42 ± 0.12
|
0.96 ± 0.28
|
1.1 ± 0.2
|
1.0 ± 0.3
|
|
LVEF (%)
|
55.9 ± 9.8
|
54.0 ± 9.0
|
55.4 ± 10.5
|
54.9 ± 8.1
|
|
Aortic valve insufficiency ≥ moderate
|
18 (8.6)
|
1 (0.5)
|
0
|
1 (0.7)
|
|
Mitral valve stenosis ≥ moderate
|
0
|
0
|
0
|
0
|
|
Mitral valve insufficiency ≥ moderate
|
6 (2.9)
|
5 (2.6)
|
3 (4.1)
|
7 (5.3)
|
|
Tricuspid valve insufficiency
|
1 (0.5)
|
7 (3.6)
|
0
|
2 (1.5)
|
|
Pulmonary arterial pressure—systolic (mmHg)
|
34.2 ± 11.6
|
|
25.7 ± 10.2
|
27.7 ± 8.5
|
Abbreviations: AV PG, aortic valve pressure gradient; EOA, effective orifice area;
LBBB, left bundle branch block; LVEDD, left ventricular end-diastolic diameter; LVEF;
left ventricular ejection fraction; LVOT, left ventricular outflow tract; RBBB, right
bundle branch block; VTI, velocity time integral.
Furthermore, hemodynamic by valve size indicates a low mean AV PG (mmHg) with an increased
EOA (cm2) after the procedure across all valve sizes stable for up to 3 years ([Fig. 1]). Compared with other sizes, ≤21 mm valves had a slightly higher transvalvular gradient
and lower EOA at discharge, and 1- and 3-year follow-up.
Fig. 1 Hemodynamic by valve size. EOA, effective orifice area; MPG, mean pressure gradient.
Quality of Life and Functional Status
In the present analysis, the SF-12v2 questionnaire was used to assess the patient's
QoL after surgery ([Supplementary Table S1], available in the online version). At 1 year after surgery, the mean SF-12v2 physical
summary score was significantly increased to 44.1 ± 9.9 points (p < 0.001) compared with baseline and further remained stable at 3-year follow-up (44.2 ± 9.8
points; p < 0.001; [Fig. 2]). Similarly, the mean SF-12v2 mental summary score significantly increased to 52.3 ± 11.6
points (p < 0.001) at 1 year and remained stable at 3-year follow-up (52.5 ± 8.6 points; p < 0.001). The physical summary scores at 1 and 3 years were as expected for the general
population mean (50.0 points), and mental summary scores were above 50.0 points, indicating
a favorable QoL in patients.
Fig. 2 Quality of life by SF-12v2 questionnaire. SF-12v2, the 12-item short-form survey
version 2.
Assessment of the functional status of the patients showed significant improvement
after surgery. At 1 and 3 years, 66.0 and 59.2% of patients had NYHA class I symptoms,
respectively, compared with baseline ([Fig. 3]). There was a significant reduction in the proportion of patients belonging to the
NYHA III/IV class at 1 year (4.5%) and 3 years (5.1%) compared with baseline (62.1%;
[Supplementary Table S2], available in the online version).
Fig. 3 NYHA functional status up to 3 years. NYHA, New York Heart Association.
At baseline, 27% (45 patients) experienced angina CCS III/IV symptoms, which decreased
to 0.6% (one patient) at 1 year after surgery. Notably, at 3 years, no patients (0%)
had angina CCS III/IV symptoms ([Supplementary Table S2], available in the online version).
Anticoagulation/Antiplatelet Therapy
Compared with baseline (19.2%), the use of post-surgical anticoagulation therapy with
various pharmacological agents increased at discharge (58.9%), 1 year (24.9%), and
3 years (24.7%) ([Table 5]). Non-vitamin K oral anticoagulants were commonly used in these patients. Conversely,
there was a decrease in patients using antiplatelet drugs at 1 year (69.2%) and 3
years (67.7%) compared with baseline (79.0%) and discharge (88.8%).
Table 5
Anticoagulation/antiplatelet therapy up to 3 years
|
n (%)
|
Baseline N = 224
|
Discharge
N = 224
|
1 year
N = 221
|
3 years
N = 158
|
|
Anticoagulants
|
43 (19.2)
|
132 (58.9)
|
50 (24.9)
|
39 (24.7)
|
|
Vitamin K antagonists
|
8 (3.6)
|
92 (41.1)
|
17 (8.5)
|
13 (8.2)
|
|
Non-vitamin K oral anticoagulants
|
22 (9.8)
|
21 (9.4)
|
31 (15.4)
|
24 (15.2)
|
|
Low molecular weight heparin
|
11 (4.9)
|
34 (15.2)
|
1 (0.5)
|
2 (1.3)
|
|
Unfractionated heparin
|
4 (1.8)
|
16 (7.1)
|
0
|
1 (0.6)
|
|
Antiplatelet drugs
|
177 (79.0)
|
199 (88.8)
|
139 (69.2)
|
107 (67.7)
|
|
Acetylsalicylic acid
|
167 (74.6)
|
187 (83.5)
|
154 (76.6)
|
112 (70.9)
|
|
Other than acetylsalicylic acid
|
30 (13.4)
|
26 (11.6)
|
18 (9.0)
|
14 (8.9)
|
Clinical Outcomes at 1 Year and 3 Years
Post-surgery outcomes within 30 days (early outcomes) included death of five patients
(2.2%), all attributed to cardiovascular causes ([Table 6]). Beyond 30 days up to 3 years outcomes (late outcomes) showed death of 25 patients
(4.6%/valve years [vy]), with 2 patients (0.2%/vy) dying of valve-related reasons,
8 patients (1.5%/vy) dying due to cardiovascular reasons, and 1 patient (0.2%/vy)
dying of unknown reasons. Freedom from all-cause mortality at 1 and 3 years was 93.0%
(95% confidence interval [CI] 89.6; 96.4) and 84.6% (95%CI 79.5; 89.7), respectively,
while freedom from valve-related mortality was 99.5% at both time points.
Table 6
Outcomes up to 3-year follow-up
|
Early (≤30 days)
n (%)
|
Late (>30 days to 3 years)
n (%/vy)[a]
|
Freedom from event 1 year
% (95%CI)
|
Freedom from event 3 years
% (95%CI)
|
|
All-cause mortality
|
5 (2.2)
|
25 (4.6)
|
93.0 (89.6; 96.4)
|
84.6 (79.5; 89.7)
|
|
Cardiovascular
|
5 (2.2)
|
8 (1.5)
|
96.3 (93.8; 98.8)
|
93.3 (89.8; 96.9)
|
|
Valve-related
|
0 (0)
|
1 (0.2)
|
99.5 (98.6; 100)
|
99.5 (98.6; 100)
|
|
Unknown
|
0 (0)
|
1 (0.2)
|
100
|
99.3 (98.2; 100)
|
|
Structural valve deterioration
|
0 (0)
|
2 (0.4)
|
99.5 (98.5; 100)
|
98.9 (97.4; 100)
|
|
Prosthetic valve endocarditis
|
0(0)
|
5 (0.9)
|
98.1 (96.2; 100)
|
97.4 (95.0; 99.7)
|
|
Prosthetic valve thrombosis
|
1 (0.4)
|
0
|
99.5 (98.6; 100)
|
99.5 (98.6; 100)
|
|
Reoperation valve- or CABG-related
|
3 (1.3)
|
3 (0.6)
|
97.7 (95.6; 99.7)
|
96.9 (94.5; 99.4)
|
|
Due to CABG
|
2 (0.9)
|
0
|
99.1 (97.8; 100)
|
99.1 (97.8; 100)
|
|
Due to aortic valve replacement
|
1 (0.4)
|
3 (0.6)
|
98.6 (97.0; 100)
|
97.8 (95.7; 100)
|
|
Reoperation due to bleeding/ tamponade
|
17 (7.6)
|
–
|
–
|
–
|
|
Unplanned percutaneous coronary intervention
|
0 (0)
|
8 (1.5)
|
98.5 (96.8; 100)
|
95.3 (92.1; 98.6)
|
|
Myocardial infarction
|
1 (0.4)
|
3 (0.6)
|
99.0 (97.7; 100)
|
97.9 (95.8; 99.9)
|
|
Bypass obstruction
|
0
|
3 (0.6)
|
99.5 (98.5; 100)
|
98.3 (96.4; 100)
|
|
Stroke
|
6 (2.7)
|
5 (0.9)
|
95.8 (93.2; 98.5)
|
94.7 (91.6; 97.8)
|
|
Permanent pacemaker implantation
|
17 (7.6)
|
7 (1.3)
|
90.3 (86.4; 94.3)
|
88.5 (84.1; 92.9)
|
Abbreviations: CABG, coronary artery bypass graft; CI, confidence interval.
Note: a
n = 224 patients with 540 valve-years; mean follow-up 2.4 ± 1.1 years.
Two patients (0.4%/vy) had SVD as a late outcome with freedom from events (FFE) 98.9%
(95%CI 97.4; 100) at 3 years. Five patients (0.9%/vy) developed endocarditis at 3
years (FFE 97.4% [95%CI 95.0; 99.7]). No cases (0%/vy) of valve thrombosis were reported
at 3 years. Furthermore, three patients (0.6%/vy) were reoperated due to AVR-related
causes (FFE 96.9 [95%CI 94.5; 99.4]). Notably, after surgery, 17 patients (7.6%) required
new PPI within 30 days, of which 12 patients (5.4%) had valve-related PPI and 7 patients
(1.3%/vy) required PPI at 3 years with FFE 90.3% (95%CI 86.4; 94.3) and 88.5% (95%CI
84.1; 92.9) at 1 and 3 years, respectively. There were no instances (0%) of unplanned
PCI and bypass obstruction within 30 days. However, eight patients (1.5%/vy) underwent
unplanned PCI, and three patients (0.6%/vy) developed bypass obstruction at 3 years.
Additionally, within 30 days, one patient (0.4) had MI, and six patients (2.7%) had
a stroke. At 3 years, three patients (0.6%/vy) developed MI, and five patients (0.9%/vy)
developed a stroke.
Discussion
The 3-year results of combined RDVAR with CABG using Edwards INTUITY Elite aortic
valve from the INCA registry demonstrated: (1) a good clinical outcome at 3 years
with 99.5% (95%CI 98.6; 100) freedom from valve-related mortality and 98.9% (95%CI
97.4; 100) freedom from SVD; (2) a stable postoperative hemodynamic performance up
to 3 years; (3) a significant improvement in the patient's QoL at 1 year (p < 0.001) and maintained up to 3 years (p < 0.001); and (4) a significant improvement in NYHA functional status up to 3 years
(p < 0.001).
Clinical Outcomes Up to 3 Years
In our analysis, the patients had high surgical risk as predicted by logistic EuroSCORE
I (7.8) and Euro SCORE II (3.5%). However, 30-day observed mortality (2.2%) of combined
RDAVR/CABG was lower than predicted, with good clinical outcomes for up to 3 years
after the procedure. Notably, there were no instances (0%) of in-hospital mortality
related to valve implantation in our study, while 2.2% all-cause mortality was observed,
which is comparable to 2.5% recorded by Taghiyev et al[12] for RDAVR using the Edwards INTUITY valve system and higher than 1.8% of in-hospital
mortality reported by Rahmanian et al[10] in their respective studies.
Moreover, after surgery, none of the patients (0%) experienced early prosthetic valve
endocarditis in our study, while five patients (0.9%/vy) developed late endocarditis,
yielding freedom from event rates of 98.1% (95% CI 96.2; 100) at 1 year and 97.4%
(95% CI 95.0; 99.7) at 3 years, respectively. Similarly, Laufer et al[15] reported a low incidence of early or late prosthetic endocarditis for combined procedures,
highlighting it as an additional advantage of rapid-deployment valves.
In our study, there was a slightly higher incidence (7.6%) of postoperative PPI within
30 days compared with 4.2% reported by Rahmanian et al for combined AVR using conventional
valves and CABG[10] and lower than reported in other publications on rapid-deployment sutureless valves.[16]
[17]
[18] However, Rahmanian et al's study also revealed a higher PPI rate (12.5%) in combined
RDAVR/CABG procedures, with lower rates observed in isolated RDAVR (4.5%), thus underscoring
the heightened risk of PPI in combined RDAVR/CABG procedures.[10] Romano et al[18] and Matthews et al[19] identified conducting system diseases such as right bundle branch block (BBB), left
BBB, first-degree atrioventricular block, left anterior hemiblock, and female gender,
as well as larger valve size, as significant contributors to postoperative PPI following
RDAVR. However, in our study, we were unable to establish a clear association between
PPI and any of the aforementioned risk factors. Although reduced operative, CPB, and
cross-clamp times are beneficial, these advantages must be weighed against the increased
rates of associated PPI as studies have noted (in the case of isolated AVR) that the
reduction in operative, CPB, and cross-clamp times does not obviously translate into
a better clinical outcome and must therefore be weighed against the higher PPI rate
which may increase the risk of endocarditis in the long term.[20]
[21] In our study, we did not explore such an association.
Surgical Outcomes and Hemodynamic Performance
The first attempt for valve implantation was successful in 221 patients (98.7%), and
only 2 patients (0.9%) required a second implantation attempt (successful). There
were no intraoperative complications recorded in our analysis. This high level of
technical success aligns with findings from other published literature.[8]
[22] The mean aortic cross-clamp time in our study was 79.4 ± 24.1 minutes (median 73.5 minutes),
and CPB time was 109.6 ± 34.5 minutes (median 104.5 minutes), which was higher compared
with the cross-clamp (67.0 minutes) and CPB time (103.2 minutes) reported by Rahmanian
et al for combined RDAVR (Edwards INTUITY Valve System) and CABG procedure.[10] Also, in their study, the mean number of arterial and venous anastomoses was 2.08 ± 1.0,
which is lower than the 3.13 ± 1.56 anastomoses required in our study. However, Gonzalez-Barbeito
et al noted in their study that 5% of patients undergoing RDAVR received one or two
grafts, while 25% received three or more grafts, which is consistent with our findings.[5]
Furthermore, in our study, the mean implanted valve size was 23.8 ± 2.1 mm (median
25mm), which was comparable to the mean valve size of 23.3 ± 1.8 mm (median 25 mm)
reported by Rahmanian et al.[10] In our analysis, combined RDAVR with CABG has demonstrated a stable hemodynamic
status over the course of 3 years. Postoperatively, the mean AV PG was reduced to
9.2 ± 3.7 mmHg at discharge, further decreasing to 8.6 ± 3.1 mmHg at 1 year and stabilizing
at 8.9 ± 4.6 mmHg by 3-year mark, compared with baseline mean AV PG (39.4 ± 13.4 mmHg).
Similarly, EOA has significantly increased to 1.90 ± 0.55 cm2 at discharge, maintained at 2.1 ± 0.5 cm2 at 1 year and 2.0 ± 0.5 cm2 at 3 years, compared with baseline EOA (0.81 ± 0.23 cm2). A similar trend of improved hemodynamic performance within 30 days and 1 year after
RDAVR was reported by several studies.[6]
[7]
[8]
[10]
[17] Moreover, the 3-year results from the TRITON trial demonstrated a significant decrease
in mean AV PG at 1 year (9.0 ± 3.6 mmHg) and 3 years (8.7 ± 4.1 mmHg) compared with
discharge (10.7 ± 4.2 mmHg), indicating sustained hemodynamic stability after combined
RAVR/CABG procedure.[8]
Along with hemodynamic benefits in our study, a noteworthy reduction in the proportion
of patients having NYHA class III/IV symptoms at 1 year (4.5%) and 3 years (5.1%)
was observed compared with baseline (62.1%). Similar improvement was also confirmed
in 3-year results of the TRITON trial, showing 53% of patients in NYHA class III or
IV at baseline, and improvement in functional class was observed in 90% of these patients
during the follow-up period,[8] indicating a consistent trend toward enhanced functional status over time.
Quality of Life
In this study, we evaluated the health-related QoL using the SF-12v2 questionnaire,
revealing a significant improvement in QoL compared with baseline in both physical
and mental health dimensions at 1 year (p < 0.001) post-surgery with further improvement at 3 years (p < 0.001). To our knowledge, this is the first report of QoL measurement based on
SF-12v2 for a combined RDAVR/CABG procedure over a 3-year period. However, findings
from the TRANSFORM US clinical trial also reported a significant improvement in QoL,
with physical health scores increasing from 41.8 ± 10.2 to 47.6 ± 9.7 (p < 0.0001) and mental health scores increasing from 51.3 ± 9.9 to 54.3 ± 8.6 (p < 0.0001) at 1 year from baseline.[17] Furthermore, a study by Borger et al compared the QoL using EQ-5D between patients
undergoing minimally invasive surgery RDAVR (Edwards INTUITY Elite bioprosthesis)
and conventional full sternotomy AVR revealing consistent EQ-5D scores from baseline
to 3 months with no difference in both groups: baseline EQ-5D scores were 0.9 ± 0.1
and 0.9 ± 0.1, and 3-month EQ-5D scores were 0.9 ± 0.1 and 0.9 ± 0.1, respectively
(p = 0.630).[23]
Since it is an industry-funded registry to evaluate the performance of Edwards INTUITY
valve system, the second commercial sutureless valve, PERCEVAL, was not considered.
