ACC San Diego 2015

Joseph E. Bavaria M.D. Roberts Professor and Vice Chief, Division of CV Surgery Hospital of the University of Pennsylvania

LV Systolic dysfunction increases perioperative mortality in AVR

▪ Morris et al; Ann Thor Surg 1993, Pereira et al; JACC 2002, Tarantini et al; EJCTS 2003

Despite this fact, AVR Patients who survive benefit with longer survival and less symptoms. This is also true for those with or without Inotropic Reserve

▪ Levy et al, JACC 2008; Tribouilloy et al, JACC 2009; Quere et al, Circ 2006

LVEF < 20% was an exclusion in the TAVI randomized studies ….. Despite the Guideline understanding that AVR with good hemodynamics is especially important in Low EF AS (avoid PPM)

Are There any

Differences between

AVR and TAVI in

patients with AS and

Low EF?

What is the Result of Low EF in TAVR?

Study Methodology

• Definitions – Low flow (LF) SVI ≤ 35 mL/M² – Low ejection fraction (LEF) LV EF ≤ 50%

– Low gradient (LG) Mean gradient ≤ 40 mmHg

• Study population included 971 patients (92%)

with evaluable echocardiograms.

• Major outcome = 2-year all cause mortality

(based on ITT).

• Multivariable analysis with Cox proportional

hazards model: – Univariate predictors of mortality (baseline and echo variables

relating to flow, pairwise analyses, adjusted models)

Impact of Left Ventricular Function on Outcomes of Transcatheter Aortic Valve Replacement and Medical Therapy in Inoperable Patients with Aortic Stenosis: Insights from The PARTNER Trial (Cohort B)

Sammy Elmariah, MD, MPH, FACC on Behalf of The PARTNER Trial Investigators

and The PARTNER Publications Office

TCT 2013 | San Francisco | October 29, 2013

PARTNER Study Design

N = 179

N = 358 Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortality

and Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials:

Individually Powered

N = 699 High Risk

Echocardiograms

Baseline

Discharge / 7-day

30-day

6-month

1-year

Key Exclusion Criteria

Anatomic

• Aortic annulus diameter on echo < 18 mm or > 25 mm

• Severe LV dysfunction (LVEF < 20%)

• Untreated CAD requiring revascularization

Clinical

• Serum creatinine > 3.0 mg/dl or dialysis dependence

• Acute myocardial infarction within 1 month

• CVA or TIA within 6 months

• Hemodynamic instability

Baseline Patient Characteristics (1) Demographics (AT)

Characteristic

TAVR ST

LVEF

<50%

(n=46)

LVEF

≥50%

(n=123)

p-value

LVEF

<50%

(n=59)

LVEF

≥50%

(n=114)

p-value

Age - yr 85 ± 8 83 ± 9 0.15 85 ± 7 82 ± 9 0.051

Male sex (%) 52.2 41.5 0.21 50.8 45.6 0.51

STS score 13.2 ± 6.4 10.5 ± 5.5 0.006 13.3 ± 5.3 11.1 ± 4.5 0.006

NYHA 0.61 0.31

II (%) 4.3 8.1 3.4 8.8

III or IV (%) 95.7 91.9 96.6 91.2

CAD (%) 73.9 65.9 0.32 78.0 71.9 0.39

Prior MI (%) 26.7 17.2 0.17 40.7 20.2 0.004

Prior PCI (%) 30.4 26.0 0.57 27.1 19.3 0.24

Prior CABG (%) 45.7 28.5 0.03 45.8 39.5 0.43

Prior BAV (%) 19.6 12.2 0.22 22.0 19.3 0.67

0

10

20

30

40

50

60

70

1/1/00 2/1/00 3/1/00 4/1/00 5/1/00 6/1/00 7/1/00 8/1/00 9/1/00 10/1/00 11/1/00 12/1/00 1/1/01

TAVR Low LVEF

TAVR High LVEF

ST Low LVEF

ST High LVEF

Change in LVEF over Time All subjects: Low EF cases improve EF well

Left

Ventr

icula

r E

jection F

raction (

%)

Ba

se

line

1 m

on

th

6 m

on

ths

1 y

ea

r

11-14% point

improvement

in LVEF

*** ***

*** ***

Paired comparisons vs baseline:

* P < 0.05

** P < 0.005

*** P < 0.0005

*

** ***

*

‡ ‡

†

Between group comparisons :

† P < 0.05

‡ P < 0.005

All-Cause Mortality (AT) Baseline LVEF (TAVR Patients): There is no difference in Survival at 1 year!!

De

ath

fro

m a

ny c

au

se

(%

)

0

20

40

60

80

Time (months)

0 3 6 9 12

46 38 35 31 30

123 107 95 92 86

Number at risk:

TAVR-LVEF < 50%

TAVR-LVEF ≥ 50%

P = 0.550

HR: 1.20 [95% CI: 0.67, 2.15]

34.8%

30.1%

TAVR - LVEF < 50% TAVR - LVEF ≥ 50%

Implications (Low EF)

Results from the inoperable PARTNER cohort B

indicate that…

• TAVR should be considered the standard of care for

patients with symptomatic severe aortic stenosis who are

not candidates for surgery irrespective of their baseline LV

function.

– Despite Higher STS score, prior CABG, and more MR ….. The

Low EF cases (20-49%; mean = 36%) did just as well!

• 14 point EF (approx 35%) improvement in EF at 1 year,

most notably in first month.

Lauten, JACC CI 2012

• 149 TAVR with LG, LEF

(<1cm², <40mmHg, <40%)

• Compared to 1153 high grad

TAVR in German registry

However ….TAVR in Low EF/LG AS

• Higher 30 d (13%) and

1 yr (37%) mortality

What about Very Low EF

and TAVI?

One-year Outcomes Following TAVI for Severe Aortic Stenosis in Elderly Patients

with Low LV Ejection Fraction

Gerhard Schymik, MD

Klinikum Karlsruhe, Germany

on behalf of the SOURCE XT Investigators

Methods

Controls EF > 30% N = 2380

1855 pts with EF ≥ 50% 525 pts with EF >30%; <50%

Very Low EF

EF ≤ 30% N = 156

* Patients with missing EF at baseline are not included in this analysis

Baseline Characteristics

Characteristics Controls N = 2380

Very Low EF N = 156

p-value

Age (mean±SD) 81.5±6.3 80.5±6.3 0.054

Female (%) 58.9 30.8 <0.0001

BMI (mean±SD) 26.8±4.9 25.8±4.4 0.017

Logistic EuroSCORE (mean±SD) 19.6±11.8 32.6±15.3 <0.0001

STS Score (mean±SD) 7.8±6.4 10.1±7.9 <0.0001

Previous Stroke (%) 8.2 6.4 0.544

Diabetes Mellitus (%) 29.2 30.1 0.786

COPD (%) 20.4 20.5 >0.999

Peripheral Vascular Disease (%) 21.0 22.4 0.685

Porcelain Aorta (%) 6.6 4.5 0.400

Renal Insufficiency (%) 28.3 34.6 0.100

Baseline Hemodynamics (echo)

44.5 51.6

0

10

20

30

40

50

60

Controls Very Low EF

Pulmonary Pressure

0.7 0.7

0.0

0.5

1.0

Controls Very Low EF

EOA

56.3

25.9

0

10

20

30

40

50

60

Controls Very Low EF

LVEF

48.5

35.0

0

10

20

30

40

50

60

Controls Very Low EF

Mean Gradient

p =0.346 p < 0.0001

p < 0.0001 p < 0.0001

Improvement in Quality of Life

12.8

18.4

20.8

11.0

16.9

19.9

0

5

10

15

20

25

Discharge 30 Days 1 Year

Change from Baseline (EQ-5D)

Controls

Very Low EF

All changes from baseline are statistically significant < 0.0001

p =0.756 p =0.532

p = 0.624

1 Year Mortality

All-Cause Mortality Cardiac Mortality

40%

60%

80%

100%

0 2 4 6 8 10 12Su

rviv

al

Months

Very Low EF Controls

40%

60%

80%

100%

0 2 4 6 8 10 12

Surv

ival

Months

Very Low EF Controls

Log-rank p =0.012

70.1%

81.5%

80.6%

89.9%

Log-rank p =0.0004

0-2 Months: Log-rank p = 0.0003

0-4 Months: Log-rank p = 0.6053

88.9%

95.6%

78.2%

88.9%

80%

85%

90%

95%

100%

0 5 10 15 20 25 30

Surv

ival

Days

Very Low EF Controls

Improvement in EF Over Time

56.3 57.4 58.2 58.7

27.6

34.2 39.3

44.1

15

25

35

45

55

65

Baseline Discharge 30 Days 1 Year

LVEF

* p<0.0001 between the two groups

All changes from baseline are statistically significant p < 0.0001 (paired t-test)

7.5

13.3

23.4

29.3

8.1

16.2

12.8

20.6

0

5

10

15

20

25

30

CardiacMortality

OverallMortality

CardiacMortality

OverallMortality

1 Y

ear

Mo

rtal

ity

Change in EF <5% Change in EF ≥5%

Controls Very Low EF

Mortality by EF Change

Conclusions

Patients with very low EF undergoing TAVI are with significantly higher risk and cardiovascular morbidity as compared to patients with EF > 30%.

Following TAVI procedure, there is a substantial improvement in functional class and the quality of life regardless of the baseline EF.

Although, very low EF improves steadily and significantly over the first year after the intervention, it is associated with significantly higher mortality at 1 year. (?? Early effect)

Failure of severe LV dysfunction to improve early after TAVI portends an increased risk of late cardiac mortality with rates twice higher compared to those who demonstrate early improvement in LV function.

What about Comparing

AVR and TAVI in Low EF?

TAVI / AVR in Low EF AS

Clavel, Circ 2010

• 83 TAVR with LEF

(not necessarily LG or LF)

• Compared to 200 SAVR

(propensity score)

• TAVR better recovery EF

• Higher iAVA with TAVR

F. Bauer, et al (Rouen, France); Echocardiography 2013

Excellent

Improvement of LVEF

in Both TAVR and

SAVR at 3 months

Propensity Matched Population:

TAVR vs SAVR with Short term

outcomes

Results Equal

More Pacemakers with TAVI

More AI with TAVI

More Transfusion with SAVR

Trend towards higher Euroscore in

AVR patients: p = 0.1 (26 vs 21)

Randomized PARTNER Trial

Predictors of Mortality and Outcomes of Therapy in Low Flow Severe Aortic Stenosis

Howard C. Herrmann, MD University of Pennsylvania, Philadelphia, PA

And the PARTNER A and B Investigators

TCT 2012 | Miami, FL | October 24, 2012: Circulation 2013

PARTNER Study Design

N = 179

N = 358 Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortality

and Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

Primary Endpoint: All-Cause Mortality at 1 yr

(Non-inferiority)

TA TAVR AVR VS

VS

N = 248 N = 104 N = 103 N = 244

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials:

Individually Powered

N = 699 High Risk

ASSESSMENT:

Transfemoral

Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

Treatment Comparison in LF and LEF (both cohorts)

2-Y

ea

r D

ea

th (

%)

0

10

20

30

40

50

60

70

80

90

Time in Days

0 60 120 180 240 300 360 420 480 540 600 660 720

76 68 62 56 53 52 49 46 44 77 58 56 54 53 50 47 46 41 34 29 26 21 20 17 17 17 17 38 32 23 18 16 13 9 9 7

Number At Risk A-TAVR A-Surgery B-TAVR B-Std Rx

Log Rank P= <.001

40.8% 37.4%

50.0%

79.9%

LF and LEF - A-TAVR LF and LEF - A-Surgery LF and LEF - B-TAVR LF and LEF - B-Std Rx

Treatment Comparison AVR and TAVI in LF, LEF, and LG (both cohorts) (Classic Low EF AS cases)

2-Y

ea

r D

ea

th (

%)

0

10

20

30

40

50

60

70

80

90

Time in Days

0 60 120 180 240 300 360 420 480 540 600 660 720

56 50 45 39 38 37 35 32 32 49 38 36 35 35 32 29 29 27 17 15 14 12 11 9 9 9 9 25 19 13 10 10 8 5 5 5

Number At Risk A-TAVR A-Surgery B-TAVR B-Std Rx

Log Rank P= 0.001

42.9%

37.1%

47.1%

80.0%

LF, LEF and LG - A-TAVR LF, LEF and LG - A-Surgery LF, LEF and LG - B-TAVR LF, LEF and LG - B-Std Rx

Results Paradoxical LF, Normal EF, and LG

0%

10%

20%

30%

40%

50%

60%

80%

90%

60 120 180 240 300 360 420 480 540 600 660 720

70%

2-Y

ea

r D

ea

th (

%)

39.7%

41.1%

56.5%

76.9%

0

log rank p= 0.003

Numbers at Risk

A – TAVR 43 39 38 34 34 33 29 26 22 A – Surgery 44 33 30 30 28 27 27 26 23 B – TAVR 23 21 19 17 15 13 11 10 10 B – Std Rx 29 22 15 10 9 9 6 5 4

LF NEF LG – A - TAVR

LF NEF LG – A - Surgery

LF NEF LG – B - TAVR

LF NEF LG – B - Std Rx

Days

AVR or TAVI should be performed in patients with Low EF (Low Flow) and severe AS

Inoperable and High Risk Low EF patients should usually receive a TAVI (STS > 8 or EuroScore > 25)

▪ Make sure there is no AI and need Big Valve (PPM)

Low Flow, Low gradient, NORMAL EF patients (Paradoxical) may be better served with TAVI