milano - outcomes with vad and transplant
TRANSCRIPT
Contemporary Outcomes with Implantable LVADs
Carmelo A. Milano, M.D. Associate Professor of Surgery
Director of Cardiac TransplantaCon and Mechanical Circulatory Support
Duke University Medical Center
Disclosures
• Consultant and Training for Thoratec Inc. • Consultant Heartware Inc. • InvesCgator Abiomed Inc.
Jessup M, Brozena S. N Engl J Med 2003;348:2007-18.
Heart Failure – Therapeutic Options
Just before death
The Projected Incidence and Cost of Heart Failure in the US
Circ Heart Fail 2013;6:606-19
Comparison of PulsaCle Flow and ConCnuous Flow LVADs as Permanent LV replacement
PF LVAD
CF LVAD
Weight (gm) 1250 390
Volume (ml) 450 63
Noise Audible Silent
Moving parts Many One
Maximal flow (l/min)*
10 10
Clinical Durability (mo)
18 ?
* at mean pressure=100 mm Hg
CF LVAD with controller and batteries CF LVAD PF LVAD
Primary Endpoint HeartMate II DesCnaCon Therapy Trial
0
10
20
30
40
50
60
Perc
en
t o
f P
ati
en
ts
CF LVAD PF LVAD
Primary Composite Endpoint (% of Patients)
P<0.001
62/134 (46%)
7/66 (11%)
Survival at 24 months, free from disabling stroke or re-operation for device repair or replacement
Hazard Ratios [95% CI]
Components:
Favors CF LVAD Favors PF LVAD
Composite: P<0.001
P<0.001
P=0.05
P=0.56
13 (10%) vs 24 (36%)
44 (33%) vs 27 (41%)
15 (11%) vs 8 (12%)
Primary Endpoint
Replacement
Death < 2 years
Disabling Stroke
0.0 0.5 1.0 1.5 2.0
NEJM 2009: Slaughter M, Rogers J, Milano C.
Improving Survival for conCnuous flow LVAD recipients
Months0 6 12 18 24
Perc
ent S
urvi
val
0102030405060708090
100
HM II BTT Miller NEJM 2007
HM II DT Slaughter NEJM 2009
HM II BTT Pagani JACC 2009
HM II BTT Starling JACC 2011
VE DT LVAD REMATCH Rose NEJM 2001
XVE DT LVAD Slaughter NEJM 2009
OMM REMATCH Rose NEJM 2001OMM INTrEPID Rogers JACC 2007
Novacor DT LVAD INTrEPID Rogers JACC 2007
HMII DT trial, recent cohort
Months0 6 12 18 24
Perc
ent S
urvi
val
0102030405060708090
100
74%
LVAD Destination Therapy (HMII Trial)
Medical Management(REMATCH, NEJM 2001)
64%
27%
8%
S. Park, C. Milano et al. CirculaCon Heart Failure 2012
ECCT and DTVAD have Comparable Survival in a Propensity-‐Matched Analysis
0 200 400 600 800 1000
0.0
0.2
0.4
0.6
0.8
1.0
Unmatched Survival
Days
Proportion Extended Criterion Transplant (n=42)
Destination Therapy LVAD (n=69)
Transplant 29 19
LVAD 42 24
Number at Riskp = 0.0637
0 200 400 600 800 1000
0.0
0.2
0.4
0.6
0.8
1.0
Matched Survival
Days
Proportion Extended Criterion Transplant (n=32)
Destination Therapy LVAD (n=32)
Transplant 20 12
LVAD 23 18
Number at Riskp = 0.897
-‐ DTVAD versus ECCT were less stable -‐ More renal insufficiency for ECCT, more stroke AEs for DT LVAD
ECCT ECCT
DTVAD DTVAD
P=0.0637 P=0.897
Unmatched Survival Propensity-‐matched Survival
HeartMate II BTT Clinical Trial FuncConal Status -‐ 6 Minute Walk
050
100150200250300350400
Baseline 1 mo 3 mo 6 mo
LVAD Duration
Met
ers
42 + 98
197 + 171
297 + 211
346 + 215
Improvement in NYHA funcConal class Heartmate II DT LVAD trial
Joseph G. Rogers , Keith D. Aaronson , Andrew J. Boyle , Stuart D. Russell , Carmelo A. Milano , Francis D. Pagani...
Con$nuous Flow Le- Ventricular Assist Device Improves Func$onal Capacity and Quality of Life of Advanced Heart Failure Pa$ents
Journal of the American College of Cardiology Volume 55, Issue 17 2010 1826 -‐ 1834
Joseph G. Rogers , Keith D. Aaronson , Andrew J. Boyle , Stuart D. Russell , Carmelo A. Milano , Francis D. Pagani...
Con$nuous Flow Le- Ventricular Assist Device Improves Func$onal Capacity and Quality of Life of Advanced Heart Failure Pa$ents
Journal of the American College of Cardiology Volume 55, Issue 17 2010 1826 -‐ 1834
Quality of Life Improvement for DesCnaCon Therapy LVAD recipients Summary Score for KCCQ Quality of Life Tool
Duke VAD Implants
0
20
40
60
80
100
120
140
2008 2009 2010 2011 2012 2013
Total VADs
Intracorporeal VADs (HM II / HVAD)
Increasing UClizaCon of Implantable LVADs as Permanent or DesCnaCon Therapy
U.S. Chronic VAD Implants vs. Heart Transplants, 2007-‐2012
Projected U.S. Chronic VAD implants by IndicaEon (Analyst EsEmates), 2013-‐2016
~1,325
~1,850 ~2,150
~2,750
~3,400
~2,200 ~2,150 ~2,200 ~2,300 ~2,300
2012 2010 2009 2008 2007
2,233
3,702
2016
5,935
2013 2015
5,089
2,193
2,895
2014
4,468
2,103
2,365
3,906
1,993
1,914
Source: Thoratec EsCmates; Average analyst projecCons for VAD market (Wells Fargo, JP Morgan, Credit Suisse, Oppenheimer)
VADs
Transplants '13-'16 CAGR
15%
25%
4%
BTT
DT
ADULT HEART TRANSPLANTS % of PaCents Bridged with Mechanical Circulatory Support* by Year and
Device Type
0
10
20
30
40
50
2005 2006 2007 2008 2009 2010
% of p
a$en
ts
Year
TAH LVAD+RVAD RVAD LVAD
* LVAD, RVAD, TAH
J Heart Lung Transplant. 2012 Oct; 31(10): 1045-‐1095
Leading Causes of Death HM II DT Trial
CAUSE OF DEATH HeartMate II (N=133)
XVE (n=59)
Hemorrhagic Stroke 12 (9%) 6 (10%)
Right Heart Failure 6 (5%) 5 (8%)
Sepsis 5 (4%) 3 (5%)
External Power InterrupCon 5 (4%) 0 (0%)
Respiratory Failure 4 (3%) 1 (2%)
Cardiac Arrest 4 (3%) 1 (2%)
Bleeding 4 (3%) 0 (0%)
MulCsystem Organ Failure 2 (2%) 4 (7%)
Pocket InfecCon 0 (0%) 3 (5%)
Device Thrombosis 2 (2%) 0 (0%)
Device Failure 3 (2%) 2 (3%)
Ischemic Stroke 1 (1%) 3 (5%)
17
Improvements in Adverse Event Rates From Early Trial to Mid Trial (first 18 mo)
0.43
0.27
0.37
0.27
0.00
0.10
0.20
0.30
0.40
0.50
Device Infection Sepsis
Early Trial Mid Trial
Infec$on (events/pt-‐yr)
** * 0.06
0.03
0.05 0.05
0.000.010.020.030.040.050.060.070.080.090.10
Hemorrhagic Ischemic
Stroke (events/pt-‐yr)
*
Park SJ, Milano CA, Tatooles AJ, et el Circ Heart Fail. 2012;5:241-‐248
DT LVAD PopulaCon
NYHA Class IV
Intermacs Levels I II III IV V VI VII
Cardiogenic Shock Stable symptoms on oral meds
The Impact of Illness Severity on MCS Outcomes
J Heart Lung Transplant 2008;27:1065-72
J Heart Lung Transplant 2010;29:1-10
INTERMACS Profile
2006-2008 (% Pts)
2012 (% Pts)
1 Critical cardiogenic Shock 34.7 16.6
2 Progressive decline 40.2 36.7
3 Stable on Inotropes 13.0 27.4
% intensely ill 87.9 80.7
4 Recurrent advanced heart failure
8.4 13.0
5 Exertion intolerant 1.3 3.0
6 Exertion limited 1.0 1.5
7 Advanced Class III 1.4 0.8 J Heart Lung Transplant 2011;30:155-23 J Heart Lung Transplant 2013;32:141-56
DT LVAD for non-‐inotrope dependent Stable Class IV heart failure
Intermacs level 4-‐7
• ROADMAP – Sponsored by Thoratec Inc – nonrandomized
• REVIVE-‐IT – Sponsored by industry and NIH – randomized
ROADMAP Trial • Nonrandomized (paCent choice) • 200 subjects at 50 sites • Study PopulaCon: INTERMACs Profile 4-‐6 (noninotrope dependent Class IV heart failure)
• Not transplant eligible • Primary Endpoint: Composite of survival and funcConal improvement (> 75 meter improvement in six minute walk) at one year
• Secondary Endpoint: overall survival, QOL, need for device replacement, adverse events
Kormos et al. J Thorac Cardiovasc Surg 2010;139:1316-1324
Survival Impact of Right Heart Failure After Continuous flow LVAD
SoluCons for RV dysfuncCon amer LVAD
• Earlier intervenCon • Surgical correcCon of tricuspid insufficiency • Pulmonary vasodilators • Less invasive mechanical support for RV
Strategies for infecCon complicaCons with LVADS
• Earlier intervenCon • Eliminate Percutaneous lead • Smaller devices • Improvement in device design/coaCng
Hazard FuncCon for Death or InfecCon among DT LVAD paCents
At Risk: 130 92 45 25
Daneshmand M et al AATS 2013
HVAD System, Heartware Inc.
• HVAD miniaturized blood pump – Pericardial placement – no abd.pocket – Provides up to 10 L/min of flow – Centrifugal design, conCnuous flow – Hybrid magneCc / hydrodynamic impeller suspension
• Thin (4.2 mm), flexible driveline with faCgue resistant cables
• FDA approved bridge to Transplant • Ongoing DesCnaCon and BIVAD trial
60
70
80
90
100
0 60 120 180 240 300 360Days Post Implant
% Survival
Event: Death (censored at transplant or recovery) ITT PopulaCon
Patients at Risk
Treatment 140 128 108 92 63 36 26
Control 499 440 370 305 228 176 127
ADVANCE Trial Secondary Outcome: Survival
Days Post Implant Treatment Control
30 98.6% 96.6%
90 95.6% 93.6%
180 93.9% 90.2%
360 90.6% 85.7%
p = .39
HVAD
Control
Endurance trial (HVAD DT trial) Comparison of Adverse Events
Heartware HVAD used as BIVAD for paCents with severe biventricular
dysfuncCon
MVAD Heartware
1/3 the size and weight of HVAD Capable of full hemodynamic support Completed animal studies at Northwestern University European clinical trial starCng Planned US clinical trial 2014 Three limb trial-‐LVAD, BIVAD, Pediatrics
Conclusions
• Permanent support with conCnuous flow LVADs for end stage paCents provides impressive survival and QOL benefits
• ReducCon of adverse events is an important focus to improve therapy with conCnuous flow LVADs
• Upcoming trials focus on earlier stage of heart failure and newer designs
Modified CMS criteria for DT LVAD • NYHA Class IV end-‐stage ventricular heart failure not suitable for heart
transplantaCon
• Failure to respond to opCmal medical management (including beta-‐blockers, and ACE inhibitors if tolerated) for at least 45 of the last 60 days (down from 60 of the prior 90 days in the earlier criteria), being balloon pump dependent for seven days, or IV inotrope dependent for 14 days
• Lem ventricular ejecCon fracCon (LVEF) <25%
• Demonstrated funcConal limitaCon with a peak oxygen consumpCon of 14 ml/kg/min (increased from 12 ml/kg/min in the previous criteria)
An esCmated 150,000 HF paCent meet these criteria in USA
Effect of ICD lead on tricuspid valve
P
RV dilaCon and dysfuncCon associated with worsening tricuspid valve insufficiency
300 Implantable
LVADs
185 Insignificant
TR
115 Significant
TR
34 Concomitant Tricuspid Procedures
81 LVADs Alone
29 Annuloplasty
Repair
5 Replacements
LVAD alone versus LVAD plus TVP
0
5
10
15
20
25
30
duration ofinotropicsupport
duration ofhospitalization
lvad alone
lvad plus tvp
Ann Thorac Surg 2011;92:1414-9
Days P<0.05
P<0.05
Two limbs in trial 1) Post MI RV failure 2) Post heart surgery