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End Stage Systolic Heart Failure,
When to Do What?
When the End May Not Be the End
Nir Uriel MD
Associate Professor of Medicine
Medical Director of Heart Failure, Heart Transplant and Mechanical
Circulatory Support Program
University of Chicago
Disclosure
• Consult and Honoraria:
– Thoratec
– HeartWare
– XDX
The Prevalence of Heart Failure
• Estimated 23 million people with HF worldwide
• United States: 5.8 million
3.1 million men, 2.7 million women
• 670 000 cases diagnosed each year with over 1 million hospitalizations and 3.4 million outpatient visits
• The healthcare cost of HF is estimated at $39.2 billion in the United States for 2010
Prevalence of Common Cardiovascular and Lung Diseases, U.S., 2004, NHLBI reportDeath from specific cardiovascular, Lung and Blood Diseases, U.S., 2004 NHLBI report
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Medical Treatment in
Heart Failure
Jorde UP. Cardiol Rev. 2006 Mar-Apr;14(2):81-7.
Cardiac-Resynchronization
Therapy in Heart Failure
N= 813; NYHA III/IV, LVEF 25%, dysynchrony, GFR 60, NT-pro BNP 1900
Johon GF et al. Care-HF N Engl J Med 2005; 352:1539-1549
1 yr survival 90% After 2.5 years 10% absolute mortality reduction with CRT
(NNT=10 to save one life)
When Medical Treatment
Reach its Limit
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Norman Shumway at Stanford
Richard Lower in Virginia
Adrian Kantrowitz in New York
Christiaan Barnard in South Africa
The Turning Point
1st Heart Transplantation
Professor Christiaan Barnard
performed the first human heart
transplant on the third of
December 1967
"For a dying man it is not a difficult decision because he knows he is at the end. If a
lion chases you to the bank of a river filled with crocodiles, you will leap into the
water, convinced you have a chance to swim to the other side."
Excellent Post Transplant
Survival
Lund et al. ISHLT 30th Adult Heart Transplant Report, JHLT, 2013
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Heart Transplant
Not for Every One
Taylor D. et al J Heart Lung Transplant. 2009 Oct;28(10):1007-22
LVAD – a New Heart Physiology
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Decompression of the Heart
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Total Adult Cardiac Transplants w Device
LVAD Bridged De Novo
The Number of LVAD BTT from the Total
OHT is Increasing
Uriel N et al. J Heart Lung Transplant. 2013 Feb;32(2):188-95
How does it Help Us?
Uriel N et al. J Heart Lung Transplant. 2013 Feb;32(2):188-95
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Functional Status – 6 Minute Walk
271 235 175 128
30 + 88
166 + 168
244 + 218
285 + 235
Pagani F et al. JACC: Vol 54, No 4, 2009.
Functional Status – NYHA Class I or II
59%
83% 82%
0%
259 213 169 120
Pagani F et al. JACC: Vol 54, No 4, 2009.
LVAD as Destination Therapy
REMATCH Trial
� Randomized clinical trial
– optimal medical therapy vs. pulsatile
flow LVAD
� Non-transplant candidates (n=129)
– EF ≤ 25%,
– peak VO2 < 12 ml/kg/min,
– or continuous infusion inotropes
� FDA approval for HM I (XVE) as destination therapy
Rose EA et al. NEJM 2001;345(20):1435-43.
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DT with Heartmate II
NEJM 2009;361(23):2241-51.
NEJM 2001;345(20):1435-43.
Improvements in DT Survival
Park, S. presented at AHA 2010, Chicago
* P value adjusted for body surface area
Fang JC. N Eng J Med. 2009 Dec 3;361(23):2282-5
Schwarzenegger A…Cameron J. Terminator 3: Rise of the Machines 2003
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Garan AR et al. J Am Coll Cardiol. 2013 May 2
LVAD AICD Cohort
Garan AR et al. J Am Coll Cardiol. 2013 May 2
VT During LVAD Support
Garan AR et al. J Am Coll Cardiol. 2013 May 2
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VT During LVAD Support
Garan AR et al. J Am Coll Cardiol. 2013 May 2
The Importance of AICD
Garan AR et al. J Am Coll Cardiol. 2013 May 2
What to Do?
Garan AR et al. J Am Coll Cardiol. 2013 May 2
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Uriel N et al. European J of Heart Failure, (2011) 13(2): 195-199
HgBA1C improvement -
Uniform Phenomenon
Uriel N et al. European J of Heart Failure, (2011) 13(2): 195-199
Change in Body Composition
Uriel N, Jorde UP. Unpublished data
Collaboration with Dr Dympna Gallagher – St. Luke’s Roosevelt Hospital
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Quality of Life on Support Today
High Frequency of Bleeding?
Uriel et al. Jour Am Col of Card. 2010;56(15):1207-1213.
Heyde, NEJM 1954Sadler, NEJM 2003;394:4
GI Bleeding and AVMs in Cardiovascular
DiseaseAortic Stenosis and Von Willebrand Factor Deficiency
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Von Wi
Mannucci P. N Engl J Med 2004;351:683-694
Normal
vessel
Vascular
Injury
Platelet-
Plug
Acquired von WillebrandsSyndrome
Uriel et al. Jour Am Col Card 2010. Vol 56 Issue 15
Crow S et al, Ann Thorac Surg. 2010 Oct;90(4):1263-9
High Sheer
forces
Structura l
change in vWFmolecule
Open location
vulnerable to proteolytic
cleavage
Poor platelet-
mediated hemostasis
GI BleedingCF-LVAD
Implantation
GI Bleeding: Within HMII
Higher speeds ���� Reduced pulsatility
Within HMII population:
Reduced pulsatility in
HMII � increased risk of
non-surgical bleeding4
Wever-Pinzon et al. Circ HF 2013. March 11 Epub.
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Narrow pulse pressureNarrow pulse pressure
Decreased Intraluminal Pressure
Dilation of the Mucosal Veins
Decreased Intraluminal Pressure
Dilation of the Mucosal Veins
Formation of AVMsFormation of AVMs
Decreased Pulsatility
Crow et al. J Thorac Cardiovasc Surg 2009. 137: 208-215
Letsou et al. JHLT 2005; 24:105-109
Wever-Pinzon et al. ISHLT 2013 Abstract #72
Progression of AI in HM-XVE
vs HMII
Pak et al. J Heart and Lung Transplant 2010 29(10).
Cowger et al. Circ HF 2010. 3 (6).
Is it Important ?
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Prevalence of Aortic Insufficiency
Bejar et al. ISHLT 2013. Abstract #250966.
Aortic Valve Opening
During LVAD Support
AV closed AV opens
AI 92% 8%
No AI 56% 44%
Sang-Woo et al. J Heart Lung Transplant. 2010 Oct;29(10):1172-6
Jorde et al. Columbia continuous flow pumps AI prospective study in press
AoV Non-Opening as Risk Factor for AI
Outcomes based
on characterization
at first echo 30
days post-implant:
67 had closed AoV
�20 dev > mild AI
37 had at least
intermittent
opening of Aov
� 2 dev > mild AI
Bejar et al. ISHLT 2013. Abstract #250966.
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High Speeds and AI Development
• High CF-LVAD Speeds
• Increased Pressure in Aorta
• Decreased Pressure in LV
• Closed AoV
• Commissural fusion of leaflet tissue1
• Deterioration of leaflet tissue1
• Aortic Insufficiency2,3, 4
• Clinically significant aortic insufficiency may progress3,4
1. Mudd et al. J Heart Lung Transplant. 2008. 27(12)
2. Pak et al. J Heart and Lung Transplant 2010 29(10)
3. Aggarwal et al. Ann Thorac Surg. 2013 95 (2)
4. Cowger et al. Circ HF 2010 3(6)
Device Thrombosis
Uriel N et al. JHLT 2013
Elevated LDH
Uriel et al. JACC 2012, 60(18):1764-75
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Elevated LDH
78 patients with 120 ramp tests
Uriel et al. JACC 2012, 60(18):1764-75
Ramp Test for Speed Optimization
Uriel et al. JACC 2012; 60, 18
Normal Ramp Test Video
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Device Thrombosis Video
LVEDD Slope and AV Closing
y = -0.2791x + 6.2564
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
8000 8400 8800 9200 9600 10000 10400 10800 11200 11600 12000
LVAD Ramp Study: Normal Patient
LVEDD
9200 rpm: AV Valve Closed
Ramp test Report
Uriel N et al. J Am Coll Cardiol. 2012 Oct 30;60(18):1764-75.
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Diagnostic Ramp Test: LVEDD Slope
LVEDD Slope
Cut-off ~ - 0.17
78 patients with 120 ramp tests
Uriel et al. JACC 2012, 60(18):1764-75
Diagnosis Algorithm
Uriel N et a l. JACC 2012
Jarvick 2000
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Do We Need Pulsatility?
Successful Pregnancy
Supported With LVAD
Sims D et al. J Heart Lung Transplant. 2011 Sep;30(9):1065-7.
Pregnancy Course (Hemodynamics)
LVAD speed
Mitral
Regurgitation LVEDD
revolutions/min cm
LVAD implant 8,600 Moderate 6.6
Week 13 and 6 days 9,000 Moderate-
Severe
5.4
Week 21 and 6 day 9,400 Moderate 5.8
Week 25 and 6 days 9,400 Severe 6.3
Week 26 and 0 days 9,600 Moderate 5.8
Week 32 and 0 days 9,800 Moderate 6.0
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Ideal Time for Referral
� NYHA III or IV plus one of the following:� Inability to walk < 1block without dyspnea
� Serum sodium < 136 mmol/L
� BUN > 40mg/dL
� Intolerant or refractory to ACE-I / ARB / BB
� Diuretic dose > 1.5mg/kd/d
� One or more CHF related hospital admissions within 6 months
� CRT non responder
� Hematocrit < 35%
Russell SD, Miller LW, Pagani FD. Advanced heart failure:
a call to action. Congest Heart Fail. 2008;14:316-321
The Future of Heart Failure
• Stem cell
• Gene expression
• Metabolic alteration
CACC 2013
Thank you !
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Quality of Life on Support Today
Cardiac Output
4-6 L
21 L
35 L
Post Discharge Time
Optimal fluid status
Higher activity demand