-The Living Aortic Valve- Repair or Else?

Ismail El-Hamamsy, MD PhD Associate Professor

Director, Aortic Surgery Division of Cardiac Surgery Montreal Heart Institute Université de Montreal

PhD Thesis – Imperial College London (2010)

-1-

THE AORTIC ROOT IS

A LIVING STRUCTURE

AORTIC ROOT PHYSIOLOGY

Dagum et al. Circulation 1999

AORTIC VALVE

El-Hamamsy et al. J Adv Res 2009

Endothelial Cells Interstitial Cells -Smooth muscle cells

-Fibroblasts

-Myofibroblasts

Aortic Side

Ventricular Side

Collagen

GAGs

Elastin

Smooth muscle actin

AORTIC VALVE

El-Hamamsy et al. Curr Vasc Pharmacol 2009

Neurofilament

AORTIC VALVE

El-Hamamsy et al. JACC 2009

THE AORTIC ROOT

LIVING STRUCTURE =

COMPLEX FUNCTIONS

Laminar flow

Excellent hemodynamics

Low thrombogenicity

Resistance to infections

OUTCOMES FOLLOWING AVR

Laminar Flow

Hemodynamics (gradients)

Thrombogenicity

Resistance to infections

Survival Valve-related complications

Quality of life

Rationale

A LIVING AORTIC VALVE SUBSTITUTE

IMPROVED CLINICALLY-RELEVANT OUTCOMES

NON-ELDERLY ADULTS

• High level of physical activity

• Quality of life

• Prolonged anticipated life expectancy

= Exposure to valve-related complications

– Degeneration + Reoperation (tissue valves)

– Bleeding + Thromboembolisms (mechanical valves)

-2-

CONVENTIONAL AVR IN THE YOUNG

= EXCESS MORTALITY

CONVENTIONAL AVR

SEVERAL ADVANTAGES

– Standardized

– Easily reproducible

– Short operative times

– Long-term data

AVR IN THE YOUNG

Kvidal et al. JACC 2000

Excess Mortality

AVR IN THE YOUNG

Kvidal et al. JACC 2000

The younger the patients are, The higher excess mortality is

MECHANICAL AVR IN THE YOUNG

Long-term outcomes after elective isolated mechanical aor tic valve

replacement in young adults

Ismail Bouhout, MSc,aLouis-Mathieu Stevens, MD, PhD,b Amine Mazine, MSc,aNancy Poirier, MD,a

Raymond Cartier, MD,aPhilippe Demers, MD,aand Ismail El-Hamamsy, MD, PhDa

Objectives: The aim of this study was to determine long-term survival and clinical outcomes after elective

isolated mechanical aortic valve replacement in young adults.

Methods: A clinical observational study wasconducted in acohort of 450 consecutiveadults lessthan 65 years

of agewho had undergoneelectiveisolated mechanical aortic valvereplacement (AVR) between 1997and 2006.

Patients who had undergone previous cardiac surgery, and those undergoing concomitant procedures or urgent

surgery wereexcluded. Follow-up was93.3% completewith amean follow-up of 9.1 3.5 years. Theprimary

end point wassurvival. Life tableanalyseswereused to determineage- and gender-matched general population

survival. Secondary end points were reoperation and valve-related complications.

Results: Overall actuarial survival at 1, 5, and 10 years was 98% 1%, 95% 1%, and 87% 1%,

respectively, which was lower than expected in the age- and gender-matched general population in Quebec.

Actuarial freedom from prosthetic valve dysfunction was 99% 0.4%, 95% 1%, and 91% 1% at

1, 5, and 10 years, respectively. Actuarial freedom from valve reintervention was 98% 1%, 96% 1%,

and 94% 1% at 1, 5 and 10 years, respectively. Actuarial survival free from reoperation at 10 years was

82% 2%. Actuarial freedom from major hemorrhage was 98% 1%, 96% 1%, and 90% 2% at

1, 5, and 10 years, respectively.

Conclusions: In young adults undergoing elective isolated mechanical AVR, survival remains suboptimal

compared with an age- and gender-matched general population. Furthermore, there isa low but constant hazard

of prosthetic valve reintervention after mechanical AVR. (J Thorac Cardiovasc Surg 2013;- :1-6)

Supplemental material is available online.

Aortic valvedisease isoneof themost common indications

for surgery in patients less than 65 years of age. However,

the ideal aortic valve substitute remains unknown. This is

partly due to the lack of data on long-term outcomes in

this specific patient population. More importantly, most

long-term studies of aortic valve replacement (AVR)

include patients at higher risk (urgent operations, concom-

itant coronary revascularization, reoperations), which

makes it more challenging to assess outcomes related to

the actual procedure.1-3 Nevertheless, recent evidence has

shown excess long-term mortality in patients undergoing

AVR compared with an age- and sex-matched general

population, and this discrepancy was most pronounced in

the youngest age group.4

A longer lifeexpectancy exposesyoung adultstoahigher

lifelong risk of prosthesis-related complicationsafter AVR,

most notably in the form of thromboembolic events,

hemorrhage, and reoperation. Bioprosthetic valves have

limited long-term durability and thereforecarry an inherent

risk of reoperation in young adults. Nevertheless, they have

alow thrombogenic risk and havetheadvantageof avoiding

anticoagulation. In contrast, mechanical prosthesesprovide

better long-term durability with low risk of prosthesis

reintervention, and are thus often considered the option of

choice in young adultswith aortic valvedisease.5Neverthe-

less, mechanical prostheses carry a thrombogenic risk and

therefore mandate long-term anticoagulation with an

associated risk of major bleeding. Although some studies

have examined long-term results after AVR, few have

focused on contemporary results of isolated mechanical

AVR in young adults.

The aim of this study was to assess long-term survival

in a contemporary series of consecutive young adults

undergoing elective isolated mechanical AVR compared

with the age- and gender-matched general population in

Quebec. The secondary objective was to describe the

occurrence of long-term valve-related complications after

AVR in this patient population.

From the Department of Cardiac Surgery,aMontreal Heart Institute, and Department

of Cardiac Surgery,bCentre Hospital ier de l’UniversitedeMontreal, Universitede

Montreal, Montreal, Canada.

Disclosures: Authors have nothing to disclose with regard to commercial support.

Received for publication July 31, 2013; revisions received Oct 5, 2013; accepted for

publication Oct 25, 2013.

Address for reprints: Ismail El-Hamamsy, MD, PhD, Department of Cardiac Surgery,

Montreal Heart Institute, 5000 Belanger St, Montreal, Quebec H1T 1C8, Canada

(E-mail: i.elhamamsy@icm-mhi .org).

0022-5223/$36.00

Copyright Ó 2013 by The American Association for Thoracic Surgery

http://dx.doi.org/10.1016/j.jtcvs.2013.10.064

The Journal of Thoracic and Cardiovascular Surgery c Volume - , Number - 1

Bouhout et al Acquired Cardiovascular Disease

AC

D

1997-2006: 469 isolated mechanical AVR <65 years

Exclusion: concomittant procedures, coronary disease, reoperations, emergencies (dissection),

active endocarditis

Mean age: 53.2 ± 9.2

Mean follow-up: 9.1 ± 3.5 years

Follow-up 95% complete (4099 patient-years)

Bouhout et al. JTCVS 2014

SURVIVAL – MECHANICAL AVR

Bouhout et al. JTCVS 2014

87%

78%

SURVIVAL FREE FROM REOPERATION

Bouhout et al. JTCVS 2014

82%

A 10 years, 1 in 5 patients is dead or reoperated

Valve-Related Complications

PROACT Trial (n=375 pts)

Puskas et al. JTCVS 2014

TISSUE AVR IN THE YOUNG

“. . .younger patients had worse than expected survival that was further diminished with insertion of a small prosthesis.”

3,049 Perimount patients; 1991-2004

Mihajlevic et al. JTCVS 2008

TISSUE AVR IN THE YOUNG

2,659 Perimount patients; 1984-2008

Bourguignon et al. Ann Thorac Surg 2015

Excess Mortality in Young Adults

-8 yrs

-20 yrs

Bourguignon et al. Ann Thorac Surg 2015

SVD and Death = Competing Risks

SVD Survival

Bourguignon et al. Eur J Cardiothorac Surg 2016

9,942 isolated AVR <65 years; 1996-2013

AVR IN THE YOUNG

Goldstone et al. NEJM 2017

AVR IN THE YOUNG

15-Year Mortality: 26-30%

Goldstone et al. NEJM 2017

15-Year Mortality: 32-36%

CONVENTIONAL AVR IN THE YOUNG

CURATIVE

PALLIATIVE

EXCESS MORTALITY IS OBSERVED

UP TO 60 YEARS OF AGE

AT THE TIME OF SURGERY

A LIVING AORTIC VALVE =

IMPROVED OUTCOMES?

-3-

ROSS PROCEDURE = IMPROVED CLINICAL

OUTCOMES

Historical Perspective

Historical Perspective

Surgical Forum 1965

ROSS PROCEDURE

THE ONLY REPLACEMENT OPERATION THAT GUARANTEES LONG-TERM

VIABILITY OF THE AORTIC VALVE/ROOT

Negative Biases

“Transforms single valve disease into double valve disease”

“High operative morbidity and mortality”

“High rate of reoperations”

SURVIVAL

SURVIVAL - ROSS

El-Hamamsy et al. Lancet 2010

SURVIVAL - ROSS

El-Hamamsy et al. Lancet 2010

ROSS

GENERAL POPULATION

SURVIVAL - ROSS

David et al. JTCVS 2010

• 1990-2004 • 212 pts • 34 +/- 9 years • Mean Fup: 10.1 yrs

SURVIVAL - ROSS

David et al. JTCVS 2014

• 1990-2004 • 212 pts • 34 +/- 9 years • Median Fup: 13.8 years

SURVIVAL

Sievers et al. Eur J Cardiothor Surg 2015

• 1990-2013 • 1779 pts (8 centers) • 45+/- 11 years • Mean Fup: 8.3 years (662 pts >10 years)

SURVIVAL

Mastrobuoni, EJCTS 2015

• 1991-2014 • 306 pts • 42+/- 9 years • Median Fup: 10.6 years

Survival Free from Reoperation

Sharabiani et al. JACC 2016

• UK National Registry • 2000-2012 • 1501 patients

Survival free from reoperation

ROSS

MECH

TISSUE

Ross vs. Mechanical AVR

Mechanical

Ross

Mazine et al. Circulation 2016

Burratto et al. JACC 2018

Ross vs. Mechanical AVR

• 1992-2016 • 392 Ross cases • Propensity-matched: 275 pairs • 43 +/- 11 years

LATE SURVIVAL - ROSS

>3600 pts

Survival - Ross

“Late mortality rates are low and resemble

the adult series age-matched population

mortality.”

5,031 adults, children; 2000-2008

Takkenberg et al. Circulation 2009

SURVIVAL

Mazine et al. JAMA Cardiol 2018

THE ROSS PROCEDURE

THE ONLY REPLACEMENT OPERATION THAT RESTORES LONG-TERM SURVIVAL

FOLLOWING AORTIC VALVE REPLACEMENT

WHAT ABOUT THE ROSS IN PATIENTS WITH

Ao REGURGITATION AND A DILATED ANNULUS?

ACHILLE’S HEEL?

Reoperation

Operative Risk

Autograft Reoperation

Klieverik et al. Eur Heart J 2007

Ross and AI

Ross and AI

Ross and AI

ROSS PROCEDURE

David TE. Circulation 2009

PARADIGM CHANGE

ANTICOAGULATION VS. REOPERATION

SURVIVAL + QUALITY OF LIFE

LATE SURVIVAL - ROSS

Autograft Reoperation

Autograft Reoperation

TECHNIQUE MATTERS

Ross Technique

MMCTS 2014

Ann Thorac Surg 2018

Tailored Approaches to AI

Mazine, El-Hamamsy et al. JACC 2018 (in press)

Tailored Ross Technique

• Trimming of infudibular muscle below the valve

• Scalloping of the autograft

Pulmonary Autograft Trimming

Tailored Ross Technique

Proximal suture line

• Place the autograft in an infra-annular position (inside the LVOT)

• Interrupted sutures

• Commissural Symmetry

Aortic vs Pulmonary Anatomy

Wall

Annulus

AorticRoot PulmonaryRoot

Tailored Ross Technique

Extra-Aortic Annuloplasty

• Extra-aortic ring annuloplasty is used if:

– AI or mixed AS/AI (with predominant AI) is the indication

– Annulus mismatch >2mm (Aortic > Pulmonary)

Extra-Aortic Annuloplasty

Basal Ring

JTCVS 2017

EJCTS 2018

Annular reduction and Stabilization

Basmadjian et al. JTCVS 2017 Lenoir et al. EJCTS 2018 (in press)

Aortic Annuloplasty

Aortic Annuloplasty

Aortic Annuloplasty

Aortic Annuloplasty

Aortic Annuloplasty

Aortic Annuloplasty

Aortic Annuloplasty

Tailored Ross Technique

Distal Suture Line

• Short autograft above STJ (or coronary anastomosis) (max 2-3mm)

• Short interposition graft if ascending aorta ≥40mm

• Careful attention to commissural symmetry

Postoperative Management

• Strict BP control in the perioperative period (max sBP 100-110mmHg)

• Home BP monitoring 6 months (max sBP 100-110mmHg)

Tailored Ross Technique

BP Remote Monitoring

Ross Procedure June 2017

Montreal Ross Program (N=356 patients)

17

36 40

36

48

73

60

46

2011 2012 2013 2014 2015 2016 2017 2018

Jan-July

Montreal Aortic Program (N=611 patients)

17

36

40

36

48

73

60

46

4 4 4 5 6 9

15

19

28

20 22

36 37 36

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Ross Procedure – N= 356 patients

Valve-Sparing/Repair – N= 255 patients

MONTREAL HEART INSTITUTE (N=356)

2011-2018

356 patients: Mean age 42 yrs (16-67 yrs)

• 15% redos (N=53)

• 60% concomittant procedures (N=208)

• 5% active endocarditis (N=17)

Operative mortality: 0.6% (n=2)

MONTREAL HEART INSTITUTE (N=356)

• The first 100 patients

– Temporary dialysis (n=5)

– Reexploration for bleeding (n=4)

– Mortality (n=2)

• The last 256 patients

– Temporary dialysis (n=3): 1.2%

– Reexploration for bleeding (n=2): <1%

–Mortality (n=0): 0%

Montreal Ross Program

2011 – 2018 : 281 consecutive Ross procedures with ≥ 1 year of follow-up

(Mean age : 46 ± 7 years)

Exclusions: - Endocarditis (n=18) - Previous AVR (n=22)

241 Ross procedures

AR group (n=73) AS group (n=168)

Mean Follow-up: 29 ± 11 months

100% complete for yearly clinical and echo follow-up

Bouhout,…,El-Hamamsy. EACTS 2018

Ross Procedure with Ring Annuloplasty

Bouhout,…,El-Hamamsy. EACTS 2018

ANY Reoperation

El-Hamamsy et al. Lancet 2010

Ross Reoperation (aortic/pulmonary)

Mazine et al. Circulation 2016

Ross Reoperation

• N= 1779 adult patients (1990-2013) • 8 centers • Mean follow-up 8.3 years

Sievers et al. EJCTS 2015

Freedom from Reoperation

1%/patient-year reoperation range

Ann Transl Med, August 2017

JTCVS, September 2017

JACC, March 2018

JTCVS, September 2018

PARADIGM CHANGE

ANTICOAGULATION VS. REOPERATION

SURVIVAL + QUALITY OF LIFE

ICM

-01-

01-2

01

2-0

8

SIMILAR OPERATIVE RISK

BETTER FREEDOM FROM VALVE-RELATED COMPLICATIONS

BETTER HEMODYNAMICS

EXCELLENT QUALITY OF LIFE

RESTORED LATE SURVIVAL

CONCLUSION

• YOUNG ADULTS = The choice of prosthesis has a direct impact on long-term prognosis

• CONVENTIONAL AVR IN THE YOUNG = Excess long-

term mortality versus general population

• ROSS PROCEDURE = Improved long-term survival and quality of life in selected patients

• IN PATIENTS WITH NON-REPAIRABLE AI, a tailored Ross procedure = Improved durability

i.elhamamsy@icm-mhi.org