heart transplantation ventricular assist device€¦ · heart transplantation & ventricular...

Heart Transplantation

&

Ventricular Assist Device

Dr Timmy WK Au

Cardiothoracic Surgery,

University of Hong Kong,

Queen Mary Hospital,

2013 Hospital Authority Convention

Relevant Financial Relationship

Disclosure Statement

I will not discuss off label use and/or investigational use of drugs/devices

The following relevant financial relationships exist related to my role in this

session: No relationships to disclose

Heart Transplantation & Ventricular Assist Device

Timmy WK Au FRCS FHKAM

Management of

“End-Stage Heart Failure”

Drugs including inotropes

Implantable devices like Automatic

Implantable Cardiac Defibrillators (AICD)

and/or CRT

Intra-Aortic Balloon Pump

ECMO

Ventricular Assist Device

Cardiac Transplantation

Surgical Therapy - What Evidence

Surgical Therapy Current recommendation Level of Evidence

Heart Transplantation Class I B

CABG for

Ischaemic Cardiomyopathy

Class I / II B

LVAD Class IIA B

Mitral Surgery Class IIB C

Surgical Ventricular

Restoration Class IIB C

Prosthetic Restrain

Device Class III C

ACC / AHA CHF guidelines Mx 2005

That was how it started

…………..in 1967

Heart transplantation

Historical background

1905 Carrel - heart transplantation in dog

1944 Medawar - concepts of organ rejection

1964 Shumway - technique of heart transplant

1967 Barnard - world first human heart transplant

1980 Stanford University - Cyclosporin A

1996 USA - 3500 heart transplant / year

NUMBER OF HEART TRANSPLANTS

REPORTED BY YEAR

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Nu

mb

er

of

Tra

ns

pla

nts

Other

EuropeNorth America

NOTE: This figure includes only the heart transplants that are

reported to the ISHLT Transplant Registry. As such, the

presented data may not mirror the changes in the number of

heart transplants performed worldwide

ISHLT 2011 ISHLT J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

AVERAGE CENTER VOLUME Heart Transplants: January 1, 2003 – June 30, 2010

45

103

30

13 246

62

0

10

20

30

40

50

60

70

80

90

100

110

1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+

Average number of heart transplants per year

Nu

mb

er

of

ce

nte

rs

0

5

10

15

20

25

30

35

40

45

50

55

Number of centers Percentage of transplants

Pe

rce

nta

ge

of

tra

ns

pla

nts


Queen Mary Hospital

Heart Transplant in HK

HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Years

Su

rviv

al (%

)

Half-life = 11.0 years

Conditional Half-life = 14.0 years

N=89,006

N at risk at 25 years = 98

HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2009)


Actuarial survival of Heart

Transplant in HK

1 year survival 87%

5 years survival 82%

10 years survival 58%

ADULT HEART TRANSPLANT RECIPIENTS:

Relative Incidence of Leading Causes of Death (Deaths: January 1992 - June 2010)

0

10

20

30

40

50

0-30 Days

(N=4,094)

31 Days –

1 Year

(N=4,028)

>1 Year – 3

Years

(N=3,166)

>3 Years –

5 Years

(N=2,674)

>5 Years –

10 Years

(N=6,273)

>10 – 15

Years

(N=3,616)

>15 Years

(N=1,753)

CAV Acute RejectionMalignancy (non-Lymph/PTLD) Infection (non-CMV)Graft Failure Multiple Organ FailureRenal Failure

Pe

rce

nta

ge

of

De

ath

s



Cumulative Incidence of Leading Causes of Death (Transplants: January 1992 - June 2009)

0%

2%

4%

6%

8%

10%

12%

14%

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Time (years)

CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Graft Failure

CMV Infection (non-CMV)

Inc

ide

nc

e o

f C

au

se

-Sp

ec

ific

De

ath

s


Post-transplant complications

Infections - bacterial, viral, fungal

Rejection

Hypertension - Cyclosporin / steroid

Hyperlipidaemia - Cyclosporin / steroid

Allograft coronary disease - 50% in 5 yrs

Renal dysfunction - Cyclosporin

Malignancy - skin, lymphoma, lung cancer

GI - ulcers, jaundice, perforation

Osteoporosis - steroid / age > 60

Psychological - anxiety, depression

Recent trend in Heart Tx

• Marginal donor heart management

• Changing trend in immunosuppression Rx

• Statins and angiotensin receptor blockers

• Reoperation for heart transplant patients

• Sophisticated LV assist device

• Xenotransplantation ???

Marginal donor heart management

Impaired heart contractility secondary to brain death triggered autonomic and cytokine storm

Optimize

• Haemodynamic, metabolic and respiratory

• Swan Ganz catheter

• Hormonal resuscitation – steroid, thyroxin, vasopressin & insulin

• Post THx ECMO support

Today’s Status of Heart Tx

Survival is excellent

Incidence of Acute Rejection is low

Long term complications are still

worrying

No growth is past 10 years

Growing demand for Mechanical

Circulatory and VAD support

289

completed HTx work-up

206 suitable

For HTx 83 delisted

120 heart

transplanted

61 died

while waiting

25

waiting list

In average, 30 % of eligible Tx patients died while

waiting for suitable donor !

Potential Heart Transplant Candidates Referred to

the Grantham Hospital for Assessment 1992-2012

ADULT HEART TRANSPLANTATION % OF PATIENTS BRIDGED WITH MECHANICAL

CIRCULATORY SUPPORT* (Transplants: 1/2000 – 12/2009)

0

10

20

30

40

50

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

% o

f p

ati

en

ts

* LVAD, RVAD, TAH ISHLT 2011 ISHLT J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

The man with the vision ….

Pagani FD ISHLT 2013

The ‘Ideal’ Blood Pump

Simple to use – able to set up & prime quickly involving minimal equipment & personnel

Minimal priming volume and connections

Gentle, atraumatic blood handling capabilities, comprised of biocompatible materials

Minimal heat generation

Minimal anticoagulant requirements

Easy to visualize during support

Easy to transport

Able to fully support cardiac output (days/weeks)

Cost effective

Pulsatile VAD - Excor

Different types of design of VADs

The Evolution of VAD Devices

Paracorporeal

Pneumatic

Pulsatile

Uni- or

Biventricular

Implantable

Electric

Pulsatile

Large

Multiple moving

parts

Implantable

Electric

Continuous flow

Axial design

Smaller

Single moving part

Implantable

Electric

Continuous flow

Centrifugal design

Smaller

Bearingless

Implantable

Electric

Continuous flow

Axial design

Smaller

Partial support

The REMATCH Trial

Randomised Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure [REMATCH]

129 patient with end-

stage CHF randomised

to permanent HeartMate

I vs optimal medical

therapy – 20 centers in

US Rose et al. REMATCH study group. N Engl J Med 2001

Survival of patients in the randomized evaluation of

mechanical assistance therapy as an alternative in CHF study.

Rose EA et al. N Engl J Med 2001

HeartMate II Initial BTT Results (n=133)

NEJM 2007;357:885-96.

Survival Following VAD Implantation

ISHLT 2009 Report

ISHLT 2013 Quarterly Report

Summary of BTT Outcomes Reference Study Enrollment

period

n Survival to Tx,

Recovery, or

Ongoing Device

Support at 180

Days

Miller, Pagani, Russell et al

NEJM 357:885-896, 2007

HM II Pivotal

Trial 3/05- 5/06 133 79%

Pagani, Miller, Russell et al

JACC 54:312-321, 2009

HM II Pivotal

Trial 3/05- 3/07 281 84%

Starling, Naka, Boyle et al

JACC 57(19): 1890-9, 2011.

Post Approval

Study

4/08 – 8/08 169 90%

John, Ann Thorac Surg 19:

1406-13. 2011

Post-trial

Study

4/08-9/10 1496 89%

Surgical Therapy – Current Status US

Surgical Therapy Current recommendation Level of Evidence

Heart Transplantation Class I B

CABG for

Ischaemic Cardiomyopathy

Class I / II B

LVAD Class IIA B

Mitral Surgery Class IIB C

Surgical Ventricular

Restoration Class IIB C

Prosthetic Restrain

Device Class III C

ACC / AHA CHF guidelines Mx 2005

Current Status - Europe

I

IIA

INTERMACS Profiles & Timing of VAD Implant

Description Time Frame

1 Patient with life-threatening hypotension despite rapidly escalating inotropic

support, critical organ hypoperfusion with increasing lactate levels and/or systemic

acidosis. “Crash and burn”

within hours

2 Patient with declining function despite IV inotropic support, may be manifest

by worsening renal function, nutritional depletion, inability to restore volume

balance. “Sliding on inotropes”

few days

3 Patient with stable blood pressure, organ function, nutrition, and symptoms on IV

inotropic support, but cannot wean off inotropes. “Dependent stability”

Elective over a

few weeks

4 Patient can be stabilized close to normal volume status but with relapses of

CHF, & fluid retention. Intensive management strategies . “Frequent flyer”

Elective over

weeks to months

5 Patient is comfortable at rest without congestive symptoms, but may have underlying refractory

elevated volume status, often with renal dysfunction. “Housebound”

Variable, depends

on nutrition, organ

function & activity

6 Patient without evidence of fluid overload is comfortable at rest and with activities, but fatigues

after the first minutes of any meaningful activity. “Walking wounded”

Variable, depends

on nutrition, organ

function,& activity

7 A placeholder for future specification, patients without recent unstable fluid balance, living

comfortably with meaningful activity limited to mild exertion. Not indicated

Bridge to

Recovery

Bridge to Recovery

Post cardiopulmonary bypass, and cannot be

weaned from the heart lung machine

Continue to deteriorate despite multiple

inotropes (at increasing dosages) and intraaortic

balloon support (IABP)

Acute decompensated heart failure secondary to

acute myocarditis / cardiomyopathy

Acute STEMI in combination with cardiogenic

shock

Bridge to

Decision

Bridge to Decision

Significant cardiac event and have questionable

neurologic status

Intervention has started prior to making a full

determination of recovery and outcome

Intervention has started prior to speaking with

the family

Bridge to Decision

Bridge to

Bridge

Bridge to a Bridge

A less expensive, or shorter termed device, is

initiated, and then switch to a long term

device once the patients condition has

stabilized (Cost considerations)

Peri-corporeal based systems are less

expensive, quicker, and require less

equipment

Opportunity to stabilize the patient -> before

better planning or transferral

CentriMag BiVentricular Support 1. Left and Right Ventricules Support

2. CentriMag cost 10% of HeartMate II

3. Proven means for Bridge to LVAD, Bridge

to transplant, Bridge to Recovery

4. Superior to ECMO

0

2

4

6

8

10

12

14

16

18

2007 2008 2009 2010 2011 2012 (up to 1/10/12)

Nu

mb

er

of

Case

ECMO operation during the year from 2007 to Aug. 2012

ECMO and CentriMag program for

Severe Cardiogenic Shock in QMH

Update of CentriMag Program

Queen Mary Hospital

9 Patients received CentriMag BiVAD since

July 2011

•3 patients successfully had heart transplantation – 29 days, 21

days, 85 days

•1 patient successfully bridge to HeartMate II implantation

•4 patients died – fungal sepsis, pulmonary HT & multi-organs

failure

•1 patient is still waiting in ICU for Heart Tx

Bridge to

Transplant

Bridge to Transplant

Bridge to Candidacy

Implantable VAD Program in QMH

HeartMate II

[Thoratec]

Update of QMH LVAD Program [BTT]

Since August 2010

9 End stage heart failure patients received LVAD

7 patients discharged home

5 patients are back to full or part time work

2 died - massive cerebral heamorrhage 6 mth ;

- multi-organ bleeding and thromboembolic

stroke 2 mth .

Contraindications for Heart Tx

Relative contraindications

• Age ≥ 65 years

• Acute myocarditis, PVD, COPD

Contraindications

• Severe pulmonary HT (fixed PVR>5 Wu, PAP>60 mm Hg)

• Psychosocial problem (alcoholism, drug addiction, severe psychotic disease etc)

• Systemic illness (amyloidosis, connective tissue diseases, neurological and muscular disorders, morbid obesity, severe cachlexia)

Destination Therapy

Refractory NYHA Class IV Heart Failure

Non-candidate for heart Tx

LVEF<25%

Failed optimal medical management for 60 of past 90 days

VO2 < 12mL/Kg/Min or need for inotropes – Hypotension,

renal dysfunction, pulmonary congestion

BSA > 1.5 m2

Absence of co-morbidities limiting survival

Destination Therapy Outcomes

Reference Study Enrollment

period

n One-Year

Survival

Two-Year

Survival

Slaughter, Rogers,

Milano et al NEJM

2009;361:2241-51

HM II Pivotal

Trial

Primary Data

Cohort

3/05- 5/07 134 68% 58%

Park, Milano, Tatooles

et al Circ HF 2012;

5:241-248

HM II Pivotal

Trial

Continued

Access

Protocol (CAP)

5/07- 3/09 281 73% 63%

Outpatient Meds Costing Transplant

Medication Dose Wholesale Monthly Cost ($)

Tacrolimus 0.5 mg BID 52.1

Tacrolimus 5 mg BID 515.96

MMF 1500 mg q12 54.42

Prednisone 15 mg q12 4.24

Acyclovir 400 mg q12 33.93

Valcyte 450 mg q12 1181.18

Mepron 1500 mg daily 555.57

Bactrim SS 1 tab daily 2.99

Nystatin susp 5 cc 4 times daily 12.24

Pantoprazole 40 mg daily 2.97

Pravastatin 20 mg HS 2.13

Lasix 20 mg daily 1.68

Lantus 1 box 227.5

Aspart 1 box 250

Norvasc 10 mg daily 2.1

Asa 81 mg daily 1.25

Colace 100 mg tid 3.25

MVT 1 tab daily 1

Yearly Wholesale Cost:

$ 34,854

LVAD

Medication Dose Wholesale Monthly Cost ($)

Amiodarone 200 mg daily 5.25

Lasix 40 mg daily 0.5

Hydraiazine 50 mg tid 15.25

Coumadin 2.5 mg daily 3

Aspirin 325 mg daily 1.25

Toprol XL 50 mg daily 21.5

Famotidine 20 mg bid 3.5

Revatio 20 mg tid 100

Lisinopril 2.5 mg daily 0.75

KCI 20 mEq bid 24.5

Colace 100 mg tid 3.25

MVT 1 tab daily 1

Lantus 1 box 227.5

Aspart 1 box 250

Yearly Wholesale Cost:

$ 7,887

Contraindications for LVAD Implant

age > ?? years

Psychological illness

Irreversible major end-organ failure

Uncertain neurological status

Severe haemodynamic instability

Major bleeding tendency

Sepsis/ prolonged mechanical ventilation

Right heart failure

Limitation of VADs

Availability and Cost

Constant changing of Models / Size / Shape

Blood component damage

Out-Patient and Long Term management

Hypertension / Stroke – Axial pump

Bleeding & Thromboembolism

Durability & mechanical failure

Infection

Peter Houghton

implanted with Jarvik

LVAD . 2000–2008.

Complications of VADs

Right ventricular failure

Bleeding

Infection

Thrombo-embolism

Haemolysis

Device failure

Intra-abdominal cx

(sensitisation with HLA antibodies)

The Future

Small and finite number of heart Tx

LVAD as initial therapy for AHF

LVAD implants will grow rapidly globally

LVAD use in less ill NYHA III patients

LVADs will evolve and improve

• Totally implanted with power supply

• Smaller and lighter

• Reduced risk of stroke and infection

• Biventricular support

Tx will be used as salvage for complications and for

those not eligible for MCS devices

Pagani FD ISHLT 2013

Summary

End Stage Heart Failure is an increasing

burden in developed countries

Heart Tx is No longer the ONLY Gold

Standard therapy for End Stage CHF

Advances in VAD design can replace Heart

Tx in certain patient groups

Cost & effectiveness of VAD support/therapy

may surpass Heart Tx within 10 years

Prof. CK Mok Dr. SW Chiu

Thank You

Visionary that Beyond the Sound Bite

Device Manufacturer Type Approval Status as of July 2009

Novacor World Heart Pulsatile. Was approved for use in North America, European Union

and Japan. Now defunct and no longer supported by

the manufacturer.

HeartMate VXE Thoratec Pulsatile. FDA approval for BTT in 2001 and DT in 2003. CE Mark

Authorized. REMATCH Trial chosen PUMP.

Rarely used anymore due to reliability concerns.

HeatMate II Thoratec Rotor driven continuous

axial flow, ball and

cup bearings.

Approved for use in North America and EU. CE Mark

Authorized. FDA warning 2008 for Lead Failure.

Recently approved by FDA in the US for Destination

Therapy (as at January 2010).

HeartMate III Thoratec Continuous flow driven

by a magnetically

suspended axial

flow rotor.

Clinical trials yet to start, uncertain future.

Incor Berlin Heart Continuous flow driven

by a magnetically

suspended axial

flow rotor.

Approved for use in European Union. Used on

humanitarian approvals on case by case basis in the

US. Entered clinical trials in the US in 2009.

Jarvik 2000 Jarvik Heart Continuous flow, axial

rotor supported by

ceramic bearings.

Currently used in the United States as a bridge to heart

transplant under an FDA-approved clinical investigation.

In Europe, the Jarvik 2000 has earned CE Mark

certification for both bridge-to-transplant and lifetime

use. Child version currently being developed.

MicroMed Debekay

VAD

MicroMed Continuous flow driven

by axial rotor

supported by

ceramic bearings.

Approved for use in the European Union. The child version

is approved by the FDA for use in children in USA.

Undergoing clinical trials in USA for FDA approval.

VentriAssist VentraCor Continuous flow driven

by a

hydrodynamically

suspended

centrifugal rotor.

Approved for use in European Union and Australia.

Company declared bankruptcy while clinical

trials for FDA approval were underway in 2009.

http://www.micromedcv.com/productprofile.htm


2007 2008 2009 2010 2011 2012 (up to 1/10/12)

Adult 0 1 2 5 3 16

Paed 3 0 1 6 7 7

0

2

4

6

8

10

12

14

16

18

Nu

mb

er

of

Case

ECMO operation during the year from 2007 to Aug. 2012

NUMBER OF HEART TRANSPLANTS

REPORTED BY YEAR

32

2 67

0 1,2

54

2,3

49 2,9

89

3,5

04

3,7

96 4,4

56

4,6

69

4,6

39

4,8

41

4,7

47

4,7

41

4,6

14

4,5

16

4,2

58

3,9

92

3,8

55

3,8

30

3,7

25

3,6

50

3,6

08

3,7

08

3,7

64

3,7

65

3,7

20

3,7

42

18

7

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Nu

mb

er

of

Tra

ns

pla

nts

NOTE: This figure includes only the heart transplants that are

reported to the ISHLT Transplant Registry. As such, the

presented data may not mirror the changes in the number of

heart transplants performed worldwide


ADULT HEART TRANSPLANTATION % OF PATIENTS BRIDGED WITH RVAD*

(Transplants: 1/2005 – 12/2009)

0

1

2

3

4

5

6

7

8

9

10

2005 2006 2007 2008 2009

Year

% o

f p

ati

en

ts

* RVAD, RVAD+LVAD ISHLT 2011 ISHLT J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Era

(Transplants: 1/1982 – 6/2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

1982-1991 (N=20,504)

1992-2001 (N=36,879)

2002-6/2009 (N=22,477)

1982-1991 vs. 1992-2001: p = 0.8460

1982-1991 vs. 2002-6/2009: p < 0.0001

1992-2001 vs. 2002-6/2009: p < 0.0001

HALF-LIFE 1982-1991: 10.2 years; 1992-2001: 10.7 years; 2002-6/2009: NA

Su

rviv

al

(%)


ADULT HEART TRANSPLANTATION Conditional Kaplan-Meier Survival by Era

(Transplants: 1/1982 – 6/2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

1982-1991 (N=16,059)

1992-2001 (N=29,287)

2002-6/2009 (N=16,686)

1982-1991 vs. 1992-2001: p = 0.0002

1982-1991 vs. 2002-6/2009: p = 0.0013

1992-2001 vs. 2002-6/2009: p = 0.2327

HALF-LIFE 1982-1991: 13.9 years; 1992-2001: 13.2 years; 2002-6/2009: NA

Su

rviv

al (%

)


Heart Tx Alternative

“It’s not an artificial heart, you still got to

have a heart and it's still got to be working."

ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by Age Group

(Transplants: 1/2002-6/2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7

Years

Su

rviv

al (%

)

18-29 (N=1,860) 30-39 (N=2,223)

40-49 (N=4,214) 50-59 (N=7,902)60-69 (N=6,010) 70+ (N=268)

All pair-wise comparisons are statistically significant at p < 0.05

except 18-29 vs. 60-69; 18-29 vs. 70+, 30-39 vs. 40-49; 30-39 vs. 50-

59 and 60-69 vs. 70+



Relative Incidence of Leading Causes of Death (Deaths: January 2000 - June 2010)

0

10

20

30

40

50

0-30 Days

(N=1,852)

31 Days –

1 Year

(N=1,814)

>1 Year – 3

Years

(N=1,402)

>3 Years –

5 Years

(N=1,285)

>5 Years –

10 Years

(N=3,802)

>10 – 15

Years

(N=3,138)

>15 Years

(N=1,752)

CAV Acute RejectionMalignancy (non-Lymph/PTLD) Infection (non-CMV)Graft Failure Multiple Organ FailureRenal Failure

Pe

rce

nta

ge

of

De

ath

s


Limitation of Cardiac Tx

Donor availability

Immune incompatibility (sensitized)

Conditional half life

Post transplant complications




the manufacturer.






cup bearings.






by a magnetically

suspended axial

flow rotor.



by a magnetically

suspended axial

flow rotor.


humanitarian approvals on case by case basis in

the US. Entered clinical trials in the US in 2009.


rotor supported by

ceramic bearings.


transplant under an FDA-approved clinical

investigation. In Europe, the Jarvik 2000 has earned

CE Mark certification for both bridge-to-transplant and

lifetime use. Child version currently being developed.

MicroMed

Debekay VAD


by axial rotor

supported by

ceramic bearings.





by a

hydrodynamically

suspended

centrifugal rotor.






Transplant Vs VAD:

Evolving & Future

Perspectives

Dr AU Wing Kuk, Timmy Consultant & Chief of Service

Cardiothoracic Surgery Department

Queen Mary Hospital

Bridge to Transplant

Severe reduction in cardiac output such that survival &

success of transplant is unlikely without MCS

Impending cardiogenic shock (despite inotropes + IABP)

resulting in acute renal / liver dysfunction

Pulmonary hypertension (PA>60) that would respond to

prolonged normalization of left atrial pressure

CentriMag versus implantable pump

Fully implantable devices allow for patient discharge

while awaiting donor organ (HeartMate II)


(Transplants: 1/1982-6/2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Years

Su

rviv

al (%

)

18-29 (N=5,580) 30-39 (N=7,898)

40-49 (N=17,714) 50-59 (N=30,967)

60-69 (N=17,187) 70+ (N=514)

HALF-LIFE 18-29: 12.3 years; 30-39: 13.2 years; 40-49: 11.7 years; 50-59: 10.5 years;

60-69: 9.5 years; 70+: 7.5 years

All pair-wise comparisons are

statistically significant at p < 0.02

except 18-29 vs. 40-49 (p=0.2807)



Cumulative Incidence of Leading Causes of Death (Transplants: January 2000 - June 2009)

0%

2%

4%

6%

8%

10%

0 1 2 3 4 5

Time (years)

CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Graft Failure

CMV Infection (non-CMV)

Inc

ide

nc

e o

f C

au

se

-Sp

ec

ific

De

ath

s


ADULT HEART TRANSPLANTS (1/2004-6/2009)

Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient age

Recipient height

Recipient weight

Donor age

Donor weight

Transplant center volume

Ischemia time

Bilirubin

Serum creatinine

PRA

Pulmonary capillary wedge pressure

Recipient PVR


ADULT HEART TRANSPLANTS (1/2004-6/2009)

Factors Not Significant for 1 Year Mortality

Recipient Factors: Prior malignancy, hospitalized, prior

pregnancy, balloon pump, diabetes, gender

Donor Factors: Clinical infection, history of diabetes,

gender, history of hypertension, cause of death, history

of malignancy

Transplant Factors: HLA mismatch, CMV mismatch,

prior transplant


ADULT HEART TRANSPLANTS (1/2004-6/2009) Relative Risk of 1 Year Mortality with 95% Confidence Limits

Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65 70

Recipient Age

p < 0.0001

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

(N=10,271) ISHLT 2011 ISHLT

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132


Donor Age

0

0.5

1

1.5

2

2.5

15 20 25 30 35 40 45 50 55

Donor Age

p < 0.0001

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity




Ischemia Time

0

0.5

1

1.5

2

30 60 90 120 150 180 210 240 270 300 330 360

Ischemia Time (minutes)

p < 0.0001Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity



AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA

0

5

10

15

20

25

30

35

40

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70+

Recipient Age

% o

f tr

an

sp

lan

ts

1982-1991 (N = 23,929)

1992-2001 (N =43,912)

2002-6/2010 (N = 31,398)

p < 0.0001



(Transplants: 1/1982-6/2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Years

Su

rviv

al (%

)

18-29 (N=5,580) 30-39 (N=7,898)

40-49 (N=17,714) 50-59 (N=30,967)

60-69 (N=17,187) 70+ (N=514)

HALF-LIFE 18-29: 12.3 years; 30-39: 13.2 years; 40-49: 11.7 years; 50-59: 10.5 years;

60-69: 9.5 years; 70+: 7.5 years

All pair-wise comparisons are

statistically significant at p < 0.02

except 18-29 vs. 40-49 (p=0.2807)


AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA

0

5

10

15

20

25

30

35

40

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70+

Recipient Age

% o

f tr

an

sp

lan

ts

1982-1991 (N = 23,929)

1992-2001 (N =43,912)

2002-6/2010 (N = 31,398)

p < 0.0001


The LVAD Current Status




the manufacturer.






cup bearings.






by a magnetically

suspended axial

flow rotor.



by a magnetically

suspended axial

flow rotor.


humanitarian approvals on case by case basis in

the US. Entered clinical trials in the US in 2009.


rotor supported by

ceramic bearings.


transplant under an FDA-approved clinical

investigation. In Europe, the Jarvik 2000 has earned

CE Mark certification for both bridge-to-transplant and

lifetime use. Child version currently being developed.

MicroMed

Debekay VAD


by axial rotor

supported by

ceramic bearings.





by a

hydrodynamically

suspended

centrifugal rotor.






The Importance of RV Function

Evaluating RV Dysfunction

LVAD Limitations

Percutaneous power supply

Risk of Stroke

Risk of Infection

Risk of Bleeding

Requirement for full sternotomy ???

Risk of mechanical failure

• Pump thrombosis

• Lead Fracture

• Controller malfunction

Summary of DT Outcomes

Reference Study Enrollment

period

n One-Year Survival

Slaughter, Rogers, Milano et al N

NEJM 2009;361:2241-51

HM II Pivotal Trial 3/05- 5/07 133 68%

Slaughter MS, presented at ISHLT

2010

HM II Pivotal Trial 5/07- 3/09 252 74%

INTERMACS Profiles & Timing of VAD Implant

Description Time Frame

1 Patient with life-threatening hypotension despite rapidly escalating inotropic

support, critical organ hypoperfusion with increasing lactate levels and/or systemic

acidosis. “Crash and burn”

within hours

2 Patient with declining function despite IV inotropic support, may be manifest

by worsening renal function, nutritional depletion, inability to restore volume

balance. “Sliding on inotropes”

few days

3 Patient with stable blood pressure, organ function, nutrition, and symptoms on IV

inotropic support, but cannot wean off inotropes. “Dependent stability”

Elective over a

few weeks

4 Patient can be stabilized close to normal volume status but with relapses of CHF, &

fluid retention. Intensive management strategies . “Frequent flyer”

Elective over

weeks to months

5

Patient is comfortable at rest without congestive symptoms, but may have

underlying refractory elevated volume status, often with renal dysfunction.

“Housebound”

Variable, depends

upon nutrition,

organ function,

and activity

6 Patient without evidence of fluid overload is comfortable at rest and with activities,

but fatigues after the first minutes of any meaningful activity. “Walking wounded”

Variable, depends

upon nutrition,

organ function,

and activity

7 A placeholder for future specification, patients without recent unstable fluid balance,

living comfortably with meaningful activity limited to mild exertion. Not indicated

heart transplantation ventricular assist device€¦ · heart transplantation & ventricular...

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