Aortic Root Enlargement: Why,

when and how

or

It is time to raise the bar and lower

the gradients!

MARK GROH MD

CHIEF, CV SURGERY

SURGICAL DIRECTOR, STRUCTURAL HEART

MISSION HOSPITAL, ASHEVILLE NC

Conflicts:

Abbott – Structural Heart Advisory Board

Patient Prosthesis Mismatch

First Described by Rahimtoola in 1978

A condition in which the prosthetic aortic

valve is smaller than the native aortic valve

By this definition, all AVR inherently result in

mismatch

Patient Prosthesis Mismatch

Assessment at time of Surgery

Echocardiographic evaluation

Difficult due to shadowing from prosthesis,

LVOT, hemodynamics, anemia

Preoperative index by manufacturer valve

table and patient size to derive EOAI,

cm2/m2

What

PPM????

Manufacturer

released predictive

EOAI for specific

valve size in patients

with varied BSA

PPM: Definitions

No PPM : EOAI > 0.85 cm2/m2

Moderate PPM: 0.65 cm2/m2 < EOAI <

0.85 cm2/m2

Severe PPM : EOAI < 0.65 cm2/m2

Fig 1

The Annals of Thoracic Surgery 2018 105 14-22 Fallon et al

10 year review of

STS database 2004-

2014

59,779 patients

over the age of 65

undergoing

isolated SAVR cross

referenced with

Medicare

database

The Annals of Thoracic Surgery 2018 105 14-22 Fallon et al

Survival

Significantly

Worse with PPM

Mod to none:

HR 1.08

95%CI 1.05-1.12

Severe to none

HR 1.32

95% CI 1.25-1.39

European Heart Journal, Volume 33, Issue 12, June 2012, Pages 1518–1529,

https://doi.org/10.1093/eurheartj/ehs003\

All Cause mortality with PPM

Meta analysis of 99 studies with 27,186 patients and 133,141

patient years

Pooled estimate for all-cause mortality: ratios demonstrate the

significant additional hazard with prosthesis–patient mismatch

Moderate 1.19 HR 95% CI 1.07-1.33

Severe 1.84 HR 95% CI 1.38-2.45

The Annals of Thoracic Surgery 2018 105 14-22 Fallon et al

CHF admissions are

higher in setting of

PPM

Moderate to No PPM

HR 1.15

95% CI 1.09-1.2

Severe to No PPM

HR1.37

95% CI 1.25-1.48

Moderate PPM

15% inc risk of admit

Severe PPM

37% inc risk of admit

The Annals of Thoracic Surgery 2018 105 14-22 Fallon et al

Redo AVR

rates are

significantly

higher in

patients with

PPM

SVD rates

Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic Heart Valves, Volume: 121, Issue: 19, Pages: 2123-

2129, DOI: (10.1161/CIRCULATIONAHA.109.901272)

Reoperation as an

indication of SVD

significantly higher

and earlier if PPM is

present

Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic Heart Valves,

Volume: 121, Issue: 19, Pages: 2123-2129, DOI: (10.1161/CIRCULATIONAHA.109.901272)

PPM leads more frequently to valve stenosis rather

than incompetence

Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic

Heart Valves, Volume: 121, Issue: 19, Pages: 2123-2129, DOI: (10.1161/CIRCULATIONAHA.109.901272)

Conclusions—These data suggest that stenosis-type SVD is an early,

PPM–related, and thus preventable phenomenon.

Incompetence-type SVD is a time-dependent, nonspecific wear

damage to bioprosthetic valves, which is not related to PPM.

Effects of PPM

Adverse affect on valve durability

Increased incidence of readmission with

CHF, less LV mass regression

Higher mortality

EOA Has a Complex Relationship With the Mean

Gradient Across the Aortic Valve and Prosthesis

There is no gradient until the

valve area is reduced by 50%.

Then, the gradient increases

gradually (red circles).

After the valve area is reduced

by 65%, the gradient increases

markedly (red line)

The Annals of Thoracic Surgery 2018 105 14-22 Fallon et al

Moderate PPM

rates have

decreased 22%

and severe 55%

over the study

dates

In 2014 46.8% of

patients had

moderate PPM

and 6.2% severe

for isolated SAVR

1) Hahn, RT, Pibarot, P, Stewart, WJ, Weissman, NJ, Gopalakrishnan, D, Keane, MG, ... & Herrmann, HC (2013). Comparison of transcatheter and surgical aortic valve replacement in severeaortic stenosis. JACC, 61(25), 2514-2521.

2) Reardon, MJ, Adams, DH, Kleiman, NS, Yakubov, SJ, Coselli, JS, Deeb, GM, ... & Heiser, J (2015). 2-year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replacement. JACC, 66(2), 113-121.

3) Pibarot P, Weissman NJ, Stewart WJ, et al. Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in high-risk patients with severe aortic stenosis: a PARTNER trial cohort-A analysis. J Am Coll Cardiol. 2014;64(13):1323-34.

4) Zorn GL III, Little SH, Tadros P, et al. Prosthesis-patient mismatch in high-risk patients with severe aortic stenosis: A randomized trial of a self-expanding prosthesis. J Thorac Cardiovasc Surg. 2016;151(4):1014-22,1023.e1-

Early effect of

severe PPM

Prosthesis–patient mismatch in

high-risk patients with severe

aortic stenosis: A randomized

trial of a self-expanding prosthesis

Zorn et al JTCVS 2016: 151 issue

14 p 1014-1023

Patients with severe PPM at risk

of mortality and kidney injury

Proprietary and confidential — do not distribute

PARTNER III – Low Risk Study 30 Day Results

1) Mack, Michael J., Martin B. Leon, Vinod H. Thourani, Raj Makkar, Susheel K. Kodali, Mark Russo, Samir R. Kapadia et al. "Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients." New England Journal of Medicine (2019).

Proprietary and confidential — do not distribute

Published Meta-analysis in TAVR

Liao et al2017

Takagi et al2016

Overall PPM 33% 35%

Moderate PPM 25% 27%

Severe PPM 11% 8%

1) Liao, Yan-biao, Yi-jian Li, Li Jun-Li, Zhen-gang Zhao, Xin Wei, Jiay-yu Tsauo, Tian-yuan Xiong, Yuan-ning Xu, Yuan Feng, and Mao Chen. "Incidence, predictors and outcome of prosthesis-patient mismatch after transcatheter aortic valve replacement: A systematic review and meta-analysis." Scientific reports 7, no. 1 (2017): 15014.

2) Takagi, Hisato, Takuya Umemoto, and ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. "Prosthesis–patient mismatch after transcatheter aortic valve implantation." The Annals of thoracic surgery 101, no. 3 (2016): 872-880.

Proprietary and confidential — do not distribute

62,125 TAVR patients

from 2014-2017

Severe PPM with

significantly increased

mortality risk and

readmission for HF at

1 year.

PPM in

TAVR

Larger Valve size and EOAI result in hemodynamic

reserve

As the EOAI in smaller valves

decrease the relative change

within valve area occurs on the

steeper portion of the curve

and results in significant

increase in gradient, increasing

turbulence, jets and

inflammation leading to

progressive stenosis.

Small valves have less “EOAI

reserve”

Aortic Root Enlargement

Results of “Hemodynamics First”

approach to SAVR

818 aortic valve replacements by single surgeon over 10 years

Exclusive use of Trifecta valve including the IDE trial

STS database and Social Security death registry

TRIFECTA: Patients Demographics (n= 818)

Variable Mean or % ± SD or

(Frequency)

Age 71.03 ± 10.12

Gender, Male 67.12% (586)

BSA, M2 2.04 ± 2.04

CVD 21.15% (173)

CVA 6.60% (54)

Prior CABG 6.48% (53)

Prior valve 11.74% (96)

Prior MI 17.36% (142)

Hypertension 86.79% (710)

Chronic lung disease 18.19% (149)

Num. Dis. Vessels 2.10 ± 1.18

PAP, Sys, mmHg 37.70 ± 10.71

EF, % 52.09 ± 10.57

5

81

237

284

161

50

19 21 23 25 27 29

Valve size, mm

0

50

100

150

200

250

300

350

No

. o

f o

bservati

on

s

Valves Sizes and Distribution, Whole Series

5

81

237

284

161

50

19 21 23 25 27 29

Valve size, mm

0

50

100

150

200

250

300

350

No

. o

f o

bservati

on

s

11%

28%

33%

21%

5%

1%

19 21 23 25 27 29

Valve Size, mm

Trifecta US Implantation

5

81

237

284

161

50

19 21 23 25 27 29

Valve size, mm

0

50

100

150

200

250

300

350

No

. o

f o

bservati

on

s

TRIFECTA: PPM Assessment, n= 818

0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.05 1.10 1.15 1.20 1.25 1.30 1.35 1.40 1.45 1.50

PPM

0

20

40

60

80

100

120

140

160

180

No.

of o

bser

vatio

ns

Expected Normal

114, 0r 13.9%

702, 0r 86.10%

2 o

r .0

24%

PPM n %None, ≥

0.85 365 88.00%

Moderate,

≤0.85 and

>0.65 52 12.23%

Severe,

≤0.65 0

PPM n %None, ≥

0.85 335 84.29%

Moderate,

≤0.85 and

>0.65 63 15.71%

Severe,

≤0.65 2 0.005%

2 26

04

12

4

14

2730

3532

2

37

29

0

52

81

6165

125

143

107

116

0

20

40

60

80

100

120

140

160

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Annular EnlargementTRF Implants

Trifecta Valve Implantation and Annular Enlargement Procedure (21%)

Variable Enl,Yes Enl, No p SD, 1 SD, 2

Age 68.60 70.58 0.1205 10.77 10.66

Gender 1.54 1.34 0.0004 0.50 0.47

HeightCm 167.78 172.57 0.0005 9.47 11.83

Valve size 24.08 24.96 0.0005 1.96 2.14

EOAi Calc 0.98 1.00 0.1742 0.11 0.13

Chronic Lung Disease 1.60 1.34 0.0452 1.28 0.97

Cerebro-vascular Disease 1.73 1.86 0.0036 0.47 0.35

Perfusion Time, min. 82.45 76.52 0.1194 24.35 33.35

Aortic ClampTime, min. 60.23 51.57 0.0004 18.74 20.69

Mean prosthesis size 24.08 24.96 0.0005 1.96 2.14

Early Mortality 0.0112 0.0183 0.646766 0.1060 0.13421

Follow-up months 35.5539 47.2360 0.001674 25.9397 32.10207

Predicted Mortality 0.0292 0.0301 0.838497 0.0254 0.03117

Female, 53.93%

Male, 66.46%

p = 0.0004

6

9

15

23

38

30

24

8

4

6

3

0

0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.05 1.10 1.15 1.20 1.25

EOAi

0

5

10

15

20

25

30

35

40

45

No

. o

f o

bs

erv

ati

on

s

Expected Normal

No EnlargementMod/severe PPM – 37%

Histogram: New EOAi

4

11

16

31 31

35

16

13

43

2

0

0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.05 1.10 1.15

New, calculated EOAi

0

5

10

15

20

25

30

35

40

No

. o

f o

bs

erv

ati

on

s

Expected Normal

After Enlargement

mod PPM 9%

Trifecta:Survival

Kaplan Meier Survival Function

0 20 40 60 80 100 120 140 160

Time, months

40%

50%

60%

70%

80%

90%

100%

Cu

mu

lati

ve P

rop

ort

ion

Su

rviv

ing

AVR, Isolated, n= 417

AVR, Complex, n= 401

Log-Rank test: p<0.0001

Survival @ 19 years

Isolated AVR: 69.39%

Complex AVR: 56.11%

1

4 4

14

21

17

14

4

2

5

3

0

0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.05 1.10 1.15 1.20 1.250

5

10

15

20

25

No

. o

f o

bs

erv

ati

on

s

Expected Normal Distribution

PPM. Severe = 0, Moderate = 9 (10.11%), None = 80 (89.9%)

2

5

15

32

27

5251

50

34

27

14

10

43

20

0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.05 1.10 1.15 1.20 1.25 1.30 1.35 1.400

10

20

30

40

50

60

No

. o

f o

bs

erv

ati

on

s

Expected Normal Distribution

PPM. Severe = 0, Moderate = 32 (9.76%), None = 274 (83.5%)

Concomitant procedures

Type n %

CABG 336 83.16%

Mitral VR* 79 19.55%

Tricuspid VR 28 6.93%

Pulmonary VR 8 1.98%

Variable Mean or % ± SD or

(Frequency)

Age 70.16 ± 10.70

Gender, Male 62.11% (259)

BSA, M2 2.02 ± 0.25

CVD 16.79% (70)

CVA 6.60% (54)

Prior CABG 4.08% (17)

Prior valve 13.91% (58)

Prior MI 9.95% (40)

Hypertension 86.79% (710)

Chronic lung dis. 18.19% (149)

EF, % 52.60 ± 10.40

Valve Sizes Distribution, AVR only (n= 417)

40

117

136

98

26

21 23 25 27 29

Valve Size, mm

0

20

40

60

80

100

120

140

160

No

. o

f o

bservatio

ns