1. Giuseppe Tarantini MD, PhD
Transcatheter Aortic Valve Implantation in Patients With Severe Left Ventricular Dysfunction
Giuseppe Tarantini MD, PhD
Assistant professor, Interventional cardiology unit
Department of Cardiac, Thoracic and Vascular Sciences
University of Padua

3. Background
Current guidelines recommend surgical AVR in patients with severe aortic stenosis (SAS) symptomatic or asymptomatic with left ventricular dysfunction (LVD) (class I).
Severe LVD is a predictor of increased surgical AVR risk leading to under treatment of these patients.
Transcatheter aortic valve implantation (TAVI) is a promising therapy for patients considered inoperable (Partner cohort B) or at high surgical risk (Partner cohort A). However, few data are available on safety and efficacy of TAVI in patients with severe LVD.

4. Aim
To assess early and mid-term outcomes of “real life” AS patients treated by TAVI with or without the presence of severe LVD in term of mortality, morbidity and LV function recovery.

5. Methods Study Sample and Study Design
Study population: 384 inoperable/high risk patients with severe aortic stenosis treated by TAVI after HEART team screening
Study design: Retrospective analysis of prospective registries
Period of enrollment: June 2007  December 2010
Centers: - Cardiology Clinic - University of Padua - Italy
- Scientific Institute San Raffaele – Milan – Italy
Devices: Edwards Sapien/Sapien XT and CoreValve Revalving System
Vascular approach: transfemoral (75%), transapical (17%), trans-subclavian (7%), transaortic (1%).
Follow-up: 9 months (range 1-36 mos).
Total TAVI population
384 pts
GROUP A (50)
LVEF ≤35%
GROUP B (334)
LVEF ≤35%

6. Methods Definitions
Device success, cardiovascular mortality, myocardial infarction, stroke, life-threatening or disabling bleeding, and vascular complications were defined according to VARC definitions.
Procedural success: device success without urgent cardiac surgery or intraprocedural death.
Thirty-day mortality: included any death within 30 days from TAVI.
In-hospital mortality: any death occurring during index hospitalization, even if the hospitalization length was longer than 30 days.
Cumulative late mortality: overall mortality, including deaths within and after 30 days.

7. Baseline Characteristics
Variables
Total Sample n=384
Group A n=50
Group B n=334
P Value
Male sex
185 (48)
29 (58)
156 (47)
0.14
Age, y, mean±SD
80±7
78±6
81±7
0.039
Body mass index, mean±SD
26.0±4.4
24.9±4.5
26.2±4.4
0.049
NYHA class III/IV
258 (67)
40 (80)
218 (65)
Congestive heart failure
152 (40)
21 (42)
131 (39)
0.71
Diabetes
103 (27)
20 (40)
83 (25)
0.024
Previous myocardial infarction
95 (25)
19 (38)
76 (23)
0.020
Previous PCI
98 (26)
15 (30)
0.44
Previous CABG
77 (20)
62 (19)
0.060
Previous stroke
61 (16)
7 (14)
54 (16)
0.70
Chronic kidney disease
183 (48)
28 (56)
155 (46)
0.21
Dialysis
11 (3)
6 (12)
5 (2)
<0.0001
Pulmonary insufficiency
132 (34)
18 (36)
114 (34)
0.80
Peripheral vasculopathy
92 (24)
13 (26)
79 (24)
0.72
Pacemaker
32 (8)
11 (22)
21 (6)
Multivessels CAD
115 (30)
22 (44)
93 (28)
Logistic euroSCORE (%), mean±SD
24.0±15.6
39.6±19.4
21.6±13.4
STS score (%), mean±SD
9.8±8.8
12.8±11.7
10.3±2.4
0.052

8. Baseline Echo Data Aortic mean gradient (mm Hg), 49.7±17.0 41.6±14.5
Variables
Total Sample n=384
Group A n=50
Group B n=334
P Value
LVEF (%), mean±SD
52.8±12.8
27.7±6.0
56.5±8.7
<0.0001
Aortic annulus (mm), mean±SD
22.7±2.0
23.3±2.0
22.6±1.9
0.041
AVA (cm2), mean±SD
0.75±0.48
0.71±0.21
0.76±0.51
0.50
AVA (cm2/m2), mean±SD
0.43±0.25
0.41±0.12
0.44±0.27
0.56
Aortic peak gradient (mm Hg), mean±SD
81.3±25.5
67.4±23.2
83.3±25.2
Aortic mean gradient (mm Hg),
49.7±17.0
41.6±14.5
50.9±17.0
<0.001
RVSP (mm Hg), mean±SD
41.9±13.7
48.3±15.2
40.9±13.2
0.001
Aortic regurgitation >2+/4
39 (10)
5 (10)
34 (10)
0.96
Mitral regurgitation >2+/4
23 (6)
18 (5)
0.20

9. Procedural Outcome CoreValve Edwards Valve 1790 (47) 205 (53) 28 (56)
Variables
Total Sample n=384
Group A n=50
Group B n=334
P Value
CoreValve
Edwards Valve
1790 (47)
205 (53)
28 (56)
22 (44)
151 (45)
183 (55)
0.2
Aortic regurgitation >2+/4 at the end of procedure
16 (4)
5 (10)
11 (3)
0.027
Coronary flow obstruction
1 (<1)
0 (0)
1.00
Device embolization
12 (3)
1 (2)
0.62
Conversion to surgery
8 (2)
7 (2)
0.97
Valve-in-valve
3 (6)
13 (4)
0.49
Tamponade
0.60
Aortic dissection
2 (<1)
Vascular complications
86 (22)
11 (22)
75 (23)
0.94
Major vascular complications
47 (12)
42 (13)
Major bleeding
35 (9)
7 (14)
28 (8)
0.20
Device success
344 (90)
41 (82)
303 (91)
0.060
Procedural success
339 (88)
298 (89)
0.14
Complete AV block
34/352 (10)
2/39 (5)
32/313 (10)
Ventricular fibrillation
15 (4)
12 (4)
0.41

10. In Hospital Outcome and Events
Variables
Total Sample n=384
Group A n=50
Group B n=334
P Value
Stroke
2 (<1)
0 (0)
1.00
Acute myocardial infarction
6 (2)
2 (4)
4 (1)
0.14
AKI requiring ultrafiltration
20/373 (5)
3/44 (7)
17/329 (5)
0.65
Sepsis
16 (4)
14 (4)
Permanent pacemaker
63/352 (18)
10/39 (26)
53/313 (17)
0.18
30-d mortality
5 (10)
9 (3)
0.010
In hospital mortality
21 (6)
7 (14)
0.004
Hospital stay, d,
10.9±11.3
12.6±16.0
10.6±10.4
0.25
At 30 days 94% of patients in NYHA I/II (p< versus baseline value).

11. Changes in LVEF in group A and group B
Panel A shows the changes in left ventricular ejection fraction (LVEF) over time in group A and group B. Panel B shows the LVEF at the same temporal steps in patients with low-flow, low-gradient aortic stenosis (group A1: LVEF ≤35% and mean aortic gradient <40 mm Hg) and in those with low-flow, high-gradient aortic stenosis (group A2: LVEF ≤35% and mean aortic gradient ≥40mm Hg).
Fraccaro C et al. Circ Cardiovasc Interv 2012;5:
Copyright © American Heart Association

12. Changes in LVEF in AS pts with severe:
LVD with low-gradient (A1) or high-gradient (A2)
A1: LVEF ≤35%; mean Ao grad <40 mm Hg
A2: LVEF ≤35%; mean Ao grad ≥40 mm Hg
Panel A shows the changes in left ventricular ejection fraction (LVEF) over time in group A and group B. Panel B shows the LVEF at the same temporal steps in patients with low-flow, low-gradient aortic stenosis (group A1: LVEF ≤35% and mean aortic gradient <40 mm Hg) and in those with low-flow, high-gradient aortic stenosis (group A2: LVEF ≤35% and mean aortic gradient ≥40mm Hg).
Fraccaro C et al. Circ Cardiovasc Interv 2012;5:
Copyright © American Heart Association

13. 1-year follow up (278 eligible pts)
Group A
Group B p
All cause death
29%
12%
0.012
Cardiovascular death
10% 6%
0.434

14. Estimated total survival by Kaplan Meier according to basal left ventricular ejection fraction (group A, solid line; group B, dotted line).
Estimated total survival by Kaplan Meier according to basal left ventricular ejection fraction (group A, solid line; group B, dotted line).
Fraccaro C et al. Circ Cardiovasc Interv 2012;5:
Copyright © American Heart Association

15. Independent predictors of cumulative late mortality
Variable HR
95% CI p
Congestive heart failure
2.69
1.64–4.40
<0.0001
Logistic euroSCORE
1.02
1.01–1.04
0.002
Moderate-to-severe periprosthetic leakage after TAVI
2.19
1.02– 4.67
0.043

16. Conclusions
TAVI appear to be a safe and effective procedure, even in “real life” patients with severe LV dysfunction leading to procedural success rates with an acceptable rate of complications and 30-day mortality.
TAVI leads to clinical improvement with a rapid partial recovery of their LV function.
Although these results are encouraging, randomized trials data are needed to determine whether this therapeutic approach is able also to improve long-term survival rates in this subgroup of patients.

17. Study Limitations Small, non-randomized, retrospective analysis.
Post-hoc analyses regarding low LVEF and/or low gradient are unpowered, therefore just hypothesis generating
No systematic evaluation of contractile reserve in pts with low gradient.
No “frailty index” was used, and it is possible that this may have affected the outcomes.

18. WHAT THE STUDY ADDS
The presence of severe left ventricular dysfunction is not infrequent, being 13% of our TAVI treated population.
Despite the fact that patients with left ventricular dysfunction were sicker and had more comorbidities, TAVI seems to be a safe and effective procedure providing a prompt and sustained improvement in clinical and left ventricular ejection function.
The presence of severe left ventricular dysfunction is not to be considered a contraindication to TAVI.