1. science
2. medicine
3. surgery
4. transplants

Definitive Therapy for Advanced Heart Failure in
2014:
Definitive
Therapy
Advanced
Heart Failure
Why LVAD
Shouldfor
Now
Be First Choice
for
in Replacement
2014:
Permanent
Why LVAD Should Now Be First Choice
Scott C. Silvestry MD
Associate Professor/Surgical Director
Cardiac Transplantation and Mechanical Circulatory Support
Program
Disclosures
Thoratec: Research funding ( material) and scientific advisor.
Heartware: Scientific advisor.
MOST devices presented are in development pre‐clinical trial use or clinical trials except where noted.
Never let the facts get in the way of a good story
Heart Transplantation






December 2, 1967
Donor: Denise Davall (24
year-old female MVA)
Recipient: Louis
Washkansky (53 year-old
male with ischemic
cardiomyopathy)
Azathioprine, Steroids,
Local radiation
POD#9 Rejection
POD#18 Death
(Pneumonia)
“Does anyone know who was the second person to fly
across the ocean?”
Norman Shumway
NUMBER OF HEART TRANSPLANTS
REPORTED BY YEAR
5000
4000
Other
Europe
North America
3500
3000
2500
2000
1500
1000
500
8
19 2
8
19 3
8
19 4
8
19 5
8
19 6
8
19 7
8
19 8
8
19 9
9
19 0
9
19 1
9
19 2
9
19 3
9
19 4
9
19 5
9
19 6
9
19 7
9
19 8
9
20 9
0
20 0
0
20 1
0
20 2
0
20 3
0
20 4
0
20 5
0
20 6
0
20 7
0
20 8
09
0
19
Number of Transplants
4500
ISHLT
2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
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
There Are Not Enough Donor Hearts
Now, cardiac transplantation is epidemiologically
trivial in heart failure management
75 year old man with two prior CABG operations
1189 days on LVAD
It must be true, I saw it on the
Internet.
VAD?
Acute Heart Failure. On ECMO preop
13
Outcomes
• 90% of patients were transplanted, recovered or had ongoing support at 6 months
• Operative 30‐day survival was 96%
• Survival was superior to that which has been previously reported with LVAD usage
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, in press 2010
Post Approval
Study
4/08 – 8/08
169
91%
Functional Status
100
90
80
70
60
50
40
30
20
10
0
6 Minute Walk Distance
100
p<0.001 over time
Both treatments
350
300
80
76
75
68
61
0
0
n= 126; 55 91 38 72 18 50 1 Baseline
3 mo
12 mo
250
200
150
100
50
0
24 mo
319
372
318
291
306
277
182 172
n= 50; 19 77 29 61 12 36 1 Baseline
LVAD Duration
NEJM 2009;361(23):2241‐51
p<0.001 over time
Both treatments
400
M e te r s
P ercen t o f p atien ts
% NYHA Class I or II
3 mo
12 mo
LVAD Duration
CF LVAD
PF LVAD
24 mo
The data we need to truly compare the therapies does not exist.
Perhaps
HeartMate II BTT Baseline INTERMACS Profiles
INTERMACS
Profile
HeartMate II
(n=169)
1
2
3
4
5-7
41 (24%)
63 (37%)
33 (20%)
21 (12%)
11 (7%)
Profile
1
2
3
4
5
6
7
Description
Critical cardiogenic shock
Progressive decline
Stable, but inotrope dependant
Recurrent advanced heart failure
Exertion tolerant
Exertion limited
Advanced NYHA III
61% of patients in the study were in profile 1 or 2.
Left Ventricular Assist Device Destination Therapy Versus Extended Criteria Cardiac
Transplant. Daneshmand, MA et al. Ann Thorac Surg 2010;89:1205-1210
ARE WE THERE YET?
1081 days,
79 s/p mvr x2 prior to implant, now 81
What Therapy?
Who would transplant this patient?
• 44 YO
• NICM 2 possibly secondary to drug use.
• Employed
• Married
• BMI>35
• Non Compliant
• ?Drug Use <6 months
LVAD is the more democratic therapy
Indications and Contraindications for
Heart Transplantation
Absolute indications in appropriate patients
Absolute contraindications
•
•
For hemodynamic compromise caused by HF
Refractory cardiogenic shock
Documented dependence on intravenous inotropic support to maintain adequate organ perfusion
Peak V˙ o2 10 mL kg1 min1 with achievement of anaerobic
metabolism
Severe symptoms of ischemia that consistently limit routine activity and are not amenable to coronary artery bypass surgery or percutaneous coronary intervention
Recurrent symptomatic ventricular arrhythmias refractory to all
therapeutic modalities
•
Relative indications
•
Relative contraindications
•
•
•
•
•
•
•
•
Peak V˙ o2 11 to 14 mL kg1 min1 (or 55% predicted) and major
limitation of the patient’s daily activities
Recurrent unstable ischemia not amenable to other intervention
Recurrent instability of fluid balance/renal
Insufficient indications
Low left ventricular ejection fraction
History of functional class III or IV symptoms of HF
Peak V˙ o2 15 mL kg1 min1 (and 55% predicted) without other indications
•
•
•
•
•
•
•
Age _72 y
Severe peripheral vascular or cerebrovascular disease
Diabetes mellitus with end‐organ damage
Severe lung, liver, or renal disease
Uncorrected abdominal aortic aneurysm (_4–6 cm)
Systemic infection (HIV, hepatitis B, Hepatitis C)
Psychosocial impairment
•
•
•
•
•
•
•
•
•
Systemic illness that will limit survival despite heart transplantation
HIV/AIDS (definition: CD4 count _200 cells/mm3)
Neoplasm other than skin or low‐grade prostate cancer that has not been cured or is not in remission
Systemic lupus erythematosus or sarcoid with multisystem involvement
Fixed pulmonary hypertension
Pulmonary vascular resistance _6 Wood units
Transpulmonary gradient _15 mm Hg
•
•
•
•
27
VAD Program Circa 2014
He’s a candidate!
We don’t discriminate!
Cardiologist
Surgeon
LVAD
•
Available when needed
•
Optimize patients
•
Does not require immunosuppresion
•
Does not require coordination with other, unrelated
programs to time.
•
Scheduled
The Real Survival For BTT LVAD Is Unknown
•
The Problem with…..
HEART TRANSPLANT?
Wait
Time
Heart
< 30 Days
All
8.7%
30 to < 90 Days
13.6%
2 6 1 Year 90 Days Month
Years to < 2 to < 6 s to < 1 to < 3 Years
Months
Year
Years
13.6%
18.6%
3 Years 5 or to < 5 More Years
Years
20.1%
9.1%
9.6%
6.9%
O
6.8% 12.2%
13.6%
18.1% 21.4%
INCONVENIENT
WAIT TIMES
10.5%
10.1%
7.7%
A
10.3%
15.6%
13.0%
18.7%
18.2%
8.1%
10.3%
6.1%
B
11.2%
14.2%
16.0%
18.1%
20.8%
6.4%
7.3%
6.2%
AB
18.2%
14.8%
12.5%
30.7%
13.6%
3.4%
2.3%
4.5%
Adult Heart Transplants
Kaplan-Meier Survival by Age Group
(Transplants: January 1982 – June 2011)
100
Median survival (years): 18-39=12.3; 40-59=10.5; 60-69=9.0; 70+=7.6
Survival (%)
80
All pair-wise comparisons were
significant at p < 0.01
60
40
Age Dependent benefit!
20
18-39 (N=15,812)
40-59 (N=55,943)
60-69 (N=20,293)
70+ (N=652)
0
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20
Years
2013
JHLT. 2013 Oct; 32(10): 951-964
As for you, my galvanized friend, you want a heart! You don't know how lucky you are not to have one. Hearts will never be practical until they can be made unbreakable. Adult Heart Transplants
% of Recipients Experiencing Any Rejection Between
Transplant Discharge and 1-Year Follow-Up by Year
60
% of patients
50
40
Pesky Rejection Episodes
30
20
10
0
2004
2005
2006
2007
2008
2009
2010
Analysis is limited to patients who were alive at the time
of the follow-up
Any rejection = Recipient was reported to (1) have at
least one acute rejection episode; or (2) have been
hospitalized for rejection.
JHLT. 2013 Oct; 32(10): 951-964
2013
Together ‐ 3368 days, 416 rounds of golf, thousands of bad jokes, countless pool hall swindles and 2 happy wives
Cost?
25
In 2007, 173,300 Medicare beneficiaries received
power wheelchairs at a total cost to themselves
and the Medicare program totaling $686 million,
part of Medicare Part B
39
What is Value in Health Care?
40
Quality of Life?
Pulled from the OR table with Severe fixed Pulmonary Hypertension.
1070 days HM ll LVAD
1 elk, 5 turkeys, 6 Deer, 10 pheasants 80x80 garden
Alaska, Florida, Vegas, the Dakotas
200 doughnuts and 12 angelfood cakes to the nurses
1 50th wedding anniversary
A book on the way
Not a VAD Patient
Actual VAD Patient
Problems?
Driveline
Thrombus
Transfusion
The Dark Side
HEART TRANSPLANT
51
Heart Transplantation
Patient
Age
Survival
Results
1
53
18 days
Pneumonia
2
58
18 months
CAV
3
52
20 months
Gastric CA
4
63
64 days
Pneumonia
5
37
12.5 years
CAV
Heart Xeno
Transplantation
James Hardy
Heart Transplantation
January 23, 1964
 Recipient: 68 year old with heart failure

failure and multiple emboli
arising from the left atrium or ventricle. Life
expectancy can be measured in hours.”
 Left leg amputation for gangrene 1/22/64
 “Patient had not regained consciousness”
 “…myocardial

Donor: “largest of 4 chimpanzees”
Heart Transplantation




“The patient developed shock. Serious
constraint developed among the five members
of our transplant team. Four were in favor of
proceeding.”
“A forceful beat was restored and supported a
blood pressure of 90-100 mmHg for 90 minutes.
The chimpanzee heart was too small for the
large man…”
“Publicity, outcry, criticism were enormous.”
“I decided to wait until Shumway transplanted a
heart in man.”
J.D. Hardy “The Academic Surgeon”
Outcomes are Improving
Age Dependent Strategy ?
Chest roentgenogram of patient 6 after implantation of 2 HeartWare HVAD ventricular assist
devices for biventricular support.
Krabatsch T et al. Circulation 2011;124:S179-S186
Copyright © American Heart Association, Inc. All rights reserved.