1. Continuous Flow LVADs: A New Physiology
Ulrich P. Jorde, MD
Associate Professor of Medicine
Medical Director,
Mechanical Circulatory Support Programs
Columbia University

2. Heartmate I
1 kilogram
2 valves
Pulsatile
- large abdominal
pocket

3. First Generation LVADs Design Limitations due to perceived need for pulsatility
Too big
Pocket infection
Too noisy

4. Does man need pulsatile flow ?
Source: Any physiology textbook

5. HM II: Axial Flow pump
342 grams
No valves
No pulse
No pocket

7. Survival HM II : 58%
Survival HM I : 23 %
Survival Med Rx: 8% ?!

8. Current 1-year success on HM II support awaiting HTX: 85%
Absolute improvement of 17%
over time WITHOUT change
in pump technology
This improvement is due to
clinical experience with a
new physiology, continous flow.
When “n” is small, IME* is big (again)
John R, Naka Y, Smedira SG, Starling R, Jorde U, Eckman P, Farrar D, Pagani F. JACC 5/2011
* IME = In My Experience

9. Case Presentation
69 year old man with h/o Afib / ICM. HM II implant 4 months prior Uncomplicated postoperative course CC: Melena Labs: Hgb 7.4 INR 1.8 plt 176 Dx: Upper GI bleed ?

10. Case Continued
EGD: Negative Colonoscopy: Negative Hgb 8.4 after 2 Unit PRBC. INR 1.2 Dx: AV malformation ?

11. Capsule Study
Why is he bleeding now? Are these AVMs new?

12. GI Bleeding and AVMs in Cardiovascular Disease
Aortic Stenosis and Von Willebrand Factor Deficiency
Sadler, NEJM 2003;394:4

13. Normal vessel Vascular Injury Platelet-Plug
Von Willebrand factor (VWF) is a large
multimeric glycoprotein
that is synthesized in endothelial cells and megakaryocytes
Normal
vessel
Vascular
Injury
Acts as a bridging molecule for platelet adhesion/ aggregation at vascular injury sites
When the vessel wall is intact, plasma von Willebrand factor that is present in a coiled structure and platelets coexist in circulating blood with minimal interactions.
von Willebrand factor and collagen fibrils localized in the subendothelial extracellular matrix.
In the event of blood vessel damage, von Willebrand factor is released from the exposed subendothelial matrix, and uncoils, in order to facilitate adhesion of circulating platelets to the lesion in synergy with collagen.
Once platelets are activated (represented by irregular margins), receptor IIb3 (as shown as yellow crosses) bind to von Willebrand factor
This event, allows IIb3 to bind platelets to the vessel wall and to others platelets that eventually lead to platelet-plug formation mediated by von Willebrand factor.
Platelet-Plug
Mannucci P. N Engl J Med 2004;351:

14. HM II Rotor Induces Shear Stress
Geisen Eur J CTS 2008: vWF deficiency in HM II recipients

15. Normalization of vW Factors After Transplant
In all 6 patients, who had VWF levels measured during HMII support and repeated after heart transplantation, there was normalization of the HMW vWF multimers levels
Statistically significant elevation in the VWF:Ag and VWF:Rco.
Uriel et al. JACC 2010 15

16. 35/79 patients had bleed requiring > 1 unit blood transfusion after POD 7
Uriel et al. JACC 2010

17. High Incidence of Bleeding During HM II Support
Recently our group reported high incidence of bleeding requiring transfusing during HM II support. With increase risk of bleeding among older patients reaching 66% of the patients.
Uriel et al. JACC 2010

18. Anticoagulation Trial Protocol Heparin postop Coumadine (INR 2-3)
ASA 81
Persantine 75 TID
5 %
CUMC Protocol Change
2007
No heparin post-op
2010
INR goal 2
ASA 81 mg
2 %

19. Should we replace vWf at time of HTX (or other major procedures) ?
Double-blind, placebo controlled
Study of VWF versus Placebo in
patients with HM II undergoing
Cardiac transplant.
Bleeding
Clotting
Sensitization
Rejection

20. Less bleeding, more clotting ?
Embolic event
Bleeding
Age
/Low albumin
vwF deficiency
Anticoagulation
Afib / Age / Female sex
Infection
Low INR
Can change
Fixed *
* Generally speaking

21. Device Thrombosis: Definition *
Device Thrombosis: Any obstructive thrombus in the device or its conduits associated with clinical symptoms of impaired pump performance (e.g. decreased pump flow, need to increase pump speed, increased power, hemolysis) or the need for thrombolytic or surgical intervention. In addition, pumps will be analyzed at Thoratec. Any severe thrombus scored as a level 3 thrombus (>50% obstruction) will be captured as an event. Hemolysis: Two consecutive plasma-free hemoglobin (PFHgb) values greater than 40 mg/dl within 24-hours of each other and an LDH value greater than 1,000 mg/dl within the same 24 - hour period.
* Supplement to: Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007;357:

22. Is this Device Thrombosis ?

23. A Case of Device Thrombosis ?
52 yo woman
HM II 24 months ago (2nd device, failed explant; initially nl LVEF deteriorated over 8 weeks)
Chronic Driveline Infection
Surveillance LDH (Plasma free Hgb 20 mg/dl) .
INR 2.2 (ASA 81/ Coumadin).
Power 6 PI 4
TTE ?

24. Device Thrombosis Role of Ramp Study
Speed optimization
Examine interaction of pump,LV cavity
and valvular function during different
flow conditions.
Optimize LVEDD / RV function
Optimize AV opening
Optimize MR
2. R/o Device thrombosis
Examine flow through device
Does LVEDD decrease appropriately ?

25. Ramp Study (Goal Speed: AV opening, no MR)
Therapeutic Anticoagulation !
R/o LV clot !
R/o AV clot !
Parasternal long axis view
Drop Speed to 8000
Acquire LVEDD, MR, AI, AV opening
Increase speed every 2 min
Assess BP LVEDD, MR, AI, AV
at each stage
Stop if:
Suction or VT
LVEDD < 3 cm
12000 rpm

26. Suspicious (? diagnostic) Ramp Test Elevated LDH =1710 and High plasma free Hgb = 20.2

27. Is this Device Thrombosis ?
LDH 1700 to 3000
Scr 1.1 to 2.3

28. The Uriel Threshold

29. Test at time of Suspicion versus Test done Predischarge for Speed Optimization
LDH 1700
LDH 320
LDH 400

30. Device Thrombosis We will see it more often in DT patients
- longer support times
- need to hold anticoagulation
- comorbidities (infection) set up prothrombotic state
Need to develop early detection & management algorythms

31. Aortic Insufficiency in HM II

32. AI due to Constant Aortic Root Pressure > 80 mmHg ?

33. Mechanism of AI Development
Aortic Insufficiency develops in HM II. Why ?
Picture Courtesy of Hiroo Takayama, MD

34. Commissural Fusion and AI in HM I Patient
Connally, Frazier et al Journal of Heart and Lung Transplantation 2003; 22:

35. Degrees of AV Fusion
Jorde et al. Columbia continuous flow pumps AI prospective study

36. De novo AI during HM II Support: 25% @ 1 Year (n=140 , Columbia)
Mechanistic observations
AI present if:
Ao root large
AV does not open
AV closed
AV opens AI
66% 8%
J Heart Lung Transplant Oct 2010

37. Mechanism of AI Development
Aortic valve does not open
Aortic valve leaflet fusion occurs
Aortic Insufficiency
Solution: Maintain device speed in a range where AV opens intermittently
Ramp Study for Device Optimization at Time of Discharge

38. Heartware: Has the future arrived ?

39. Heartware 91% 6 months survival in BTT trial
Easier implant ? No sternotomy ?
Less bleeding ?
Interference with ICD leads ?
vW deficiency : Yes !
Thrombus formation

40. Understanding complications translates into better outcomes !
Criteria for DT: Class IIIb/IV systolic CHF Failing OMM (45 /60 days) No irreversible endorgan dysfunction (i.e. HD) Motivated patient who can manage device.
Park SJ, Milano C, Tatooles AJ et al. AHA 2010

41. VAD Volume Growth @ Columbia
11 long term VADs
in Jan 2012
HM II DT approval
10% DT % DT
2016
100 Long Term
80% DT
* projected

42. Continuous-Flow LVAD Destination Therapy Versus Orthotopic Heart Transplantation in Patients above 65 Years of Age
DT patients
- Not OHT candidate
- Median age 73 yrs
- LVEF 15%
- CI 1.8 l/min
- 58% inotrop
S. Melnitchouk, U. Jorde, H. Takayama, N. Uriel, P. Colombo,
J. Yang, D. Mancini, Y. Naka. ISHLT 2011

43. Device of the Future Current actual pumps already adequate ?
Driveline needs to go (No infection, no prothrombotic state, less emboli)
Smart software permitting AV opening and rpm increase with exercise
Smaller, lighter batteries – cellphone charger

44. Thank you !
Yoshifumi Naka, MD
LVAD Team Columbia