Ventricular assist devices (VADs) are implanted in patients with a diseased ventricle to maintain peripheral perfusion as a bridge-to-transplant or as destination therapy. However, some patients with continuous flow VADs (e.g., HeartMate II (HMII)) have experienced gastrointestinal (GI) bleeding, in part caused by the proteolytic cleavage or mechanical destruction of von Willebrand factor (vWF), a clotting glycoprotein. in vitro studies were performed to measure the flow located within the HMII outlet cannula under both steady and physiological conditions using particle image velocimetry (PIV). Under steady flow, a mock flow loop was used with the HMII producing a flow rate of 3.2 L/min. The physiological experiment included a pulsatile pump operated at 105 BPM with a ventricle filling volume of 50 mL and in conjunction with the HMII producing a total flow rate of 5.0 L/min. Velocity fields, Reynolds normal stresses (RNSs), and Reynolds shear stresses (RSSs) were analyzed to quantify the outlet flow's potential contribution to vWF degradation. Under both flow conditions, the HMII generated principal Reynolds stresses that are, at times, orders of magnitude higher than those needed to unfurl vWF, potentially impacting its physiological function. Under steady flow, principal RNSs were calculated to be approximately 500 Pa in the outlet cannula. Elevated Reynolds stresses were observed throughout every phase of the cardiac cycle under physiological flow with principal RNSs approaching 1500 Pa during peak systole. Prolonged exposure to these conditions may lead to acquired von Willebrand syndrome (AvWS), which is accompanied by uncontrollable bleeding episodes.

References

1.
Mozaffarian
,
D.
,
Benjamin
,
E.
,
Go
,
A.
,
Arnet
,
D.
,
Blaha
,
M.
,
Cushman
,
M.
,
de Ferranti
,
S.
,
Després
,
J.-P.
,
Fullerton
,
H.
,
Howard
,
V.
,
Huffman
,
M.
,
Judd
,
S.
,
Kissela
,
B.
,
Lackland
,
D.
,
Lichtma
,
J.
,
Lisabeth
,
L.
,
Liu
,
S.
,
Mackey
,
R.
,
Matchar
,
D.
,
McGuire
,
D.
,
Mohler
,
E.
,
Moy
,
C.
,
Muntner
,
P.
,
Mussolino
,
M.
,
Nasir
,
K.
,
Neumar
,
R.
,
Nichol
,
G.
,
Palaniappan
,
L.
,
Pandey
,
D.
,
Reeves
,
M.
,
Rodriguez
,
C.
,
Sorlie
,
P.
,
Stein
,
J.
,
Towfighi
,
A.
,
Turan
,
T.
,
Virani
,
S.
,
Willey
,
J.
,
Woo
,
D.
,
Yeh
,
R.
, and
Turner
,
M.
,
2015
, “
Heart Disease and Stroke Statistics—At-a-Glance
,”
Am. Heart Assoc.
,
1
(
1
), pp.
7
10
.
2.
Colvin
,
M.
,
Smith
,
J. M.
,
Skeans
,
M. A.
,
Edwards
,
L. B.
,
Uccellini
,
K.
,
Snyder
,
J. J.
,
Israni
,
A. K.
, and
Kasiske
,
B. L.
,
2017
, “
OPTN/SRTR 2015 Annual Data Report: Heart
,”
Am. J. Transplant.
,
17
(Suppl. 1), pp.
1
71
.
3.
Frazier
,
O. H.
, and
Parnis
,
S. M.
,
2014
, “
Ventricular Assist Devices
,”
Organ Transplantation
,
A. D.
Kirk
,
S. J.
Knechtle
,
C. P.
Larsen
,
J. C.
Madsen
,
T. C.
Pearson
, and
S. A.
Webber
, eds.,
Wiley
, New York, pp.
145
151
.
4.
De Biasi
,
A. R.
,
Manning
,
K. B.
, and
Salemi
,
A.
,
2015
, “
Science for Surgeons: Understanding Pump Thrombogenesis in Continuous-Flow Left Ventricular Assist Devices
,”
J. Thorac. Cardiovasc. Surg.
,
149
(
3
), pp.
667
673
.
5.
Meyer
,
A. L.
,
Malehsa
,
D.
,
Budde
,
U.
,
Bara
,
C.
,
Haverich
,
A.
, and
Strueber
,
M.
,
2014
, “
Acquired von Willebrand Syndrome in Patients With a Centrifugal or Axial Continuous Flow Left Ventricular Assist Device
,”
JACC Heart Failure
,
2
(
2
), pp.
141
145
.
6.
Chen
,
Z.
,
Mondal
,
N. K.
,
Ding
,
J.
,
Koenig
,
S. C.
,
Slaughter
,
M. S.
, and
Wu
,
Z. J.
,
2016
, “
Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor
,”
Artif. Organs
,
40
(
7
), pp.
659
668
.
7.
Vergauwe
,
R. M. A.
,
Uji-I
,
H.
,
De Ceunynck
,
K.
,
Vermant
,
J.
,
Vanhoorelbeke
,
K.
, and
Hofkens
,
J.
,
2014
, “
Shear Stress-Induced Conformational Changes of von Willebrand Factor in a Water Glycerol Mixture Observed With Single Molecule Microscopy
,”
J. Phys. Chem. B
,
118
(
21
), pp.
5660
5669
.
8.
Reininger
,
A. J.
,
2015
, “
The Function of Ultra-Large von Willebrand Factor Multimers in High Shear Flow Controlled by ADAMTS13
,”
Hamostaseologie
,
35
(
3
), pp.
225
233
.
9.
Chan
,
C. H. H.
,
Pieper
,
I. L.
,
Fleming
,
S.
,
Friedmann
,
Y.
,
Foster
,
G.
,
Hawkins
,
K.
,
Thornton
,
C. A.
, and
Kanamarlapudi
,
V.
,
2014
, “
The Effect of Shear Stress on the Size, Structure, and Function of Human von Willebrand Factor
,”
Artif. Organs
,
38
(
9
), pp.
741
750
.
10.
Gogia
,
S.
, and
Neelamegham
,
S.
,
2015
, “
Role of Fluid Shear Stress in Regulating VWF Structure, Function and Related Blood Disorders
,”
Biorheology
,
52
, pp.
319
335
.
11.
Chiu
,
W.-C.
,
Slepian
,
M. J.
, and
Bluestein
,
D.
,
2014
, “
Thrombus Formation Patterns in the HeartMate II VAD-Clinical Observations Can Be Predicted by Numerical Simulations
,”
ASAIO J.
,
60
(
2
), pp.
237
240
.
12.
Nascimbene
,
A.
,
Neelamegham
,
S.
,
Frazier
,
O. H.
,
Moake
,
J. L.
, and
Dong
,
J. F.
,
2016
, “
Acquired von Willebrand Syndrome Associated With Left Ventricular Assist Device
,”
Blood
,
127
(
25
), pp.
3133
3141
.
13.
Tiede
,
A.
,
Rand
,
J. H.
,
Budde
,
U.
,
Ganser
,
A.
, and
Federici
,
A. B.
,
2011
, “
How I Treat the Acquired von Willebrand Syndrome
,”
Blood
,
117
(
25
), pp.
29
31
.
14.
Tsai
,
H. M.
,
Sussman
,
I. I.
, and
Nagel
,
R. L.
,
1994
, “
Shear Stress Enhances the Proteolysis of von Willebrand Factor in Normal Plasma
,”
Blood
,
83
(
8
), pp.
2171
2179
.
15.
Miller
,
L. W.
,
Pagani
,
F. D.
,
Russell
,
S. D.
,
John
,
R.
,
Boyle
,
A. J.
,
Aaronson
,
K. D.
,
Conte
,
J. V.
,
Naka
,
Y.
,
Mancini
,
D.
,
Delgado
,
R. M.
,
Macgillivray
,
T. E.
,
Farrar
,
D. J.
, and
Frazier
,
O. H.
,
2007
, “
Use of a Continuous-Flow Device in Patients Awaiting Heart Transplantation
,”
N. Engl. J. Med.
,
9
(
357
), pp.
885
896
.
16.
Sheikh
,
F. H.
, and
Russell
,
S. D.
,
2011
, “
HeartMate II Continuous-Flow Left Ventricular Assist System
,”
Expert Rev. Med. Devices
,
8
(
1
), pp.
11
21
.
17.
Starling
,
R.
,
Naka
,
Y.
,
Boyle
,
A.
,
Gonzalez-Stawinski
,
G.
,
John
,
R.
,
Jorde
,
U.
,
Russel
,
S.
,
Conte
,
J.
,
Aaronson
,
K.
,
McGee
,
E.
, Jr.
,
Cotts
,
W.
,
DeNofrio
,
D.
,
Pham
,
D.
,
Farrar
,
D.
, and
Pagani
,
F.
,
2011
, “
Results of the Post-U.S. Food and Drug Administration-Approval Study With a Continuous Flow Left Ventricular Assist Device as a Bridge to Heart Transplantation: A Prospective Study Using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)
,”
J. Am. Coll. Cardiol.
,
57
(
19
), pp.
1890
1898
.
18.
Schüle
,
C. Y.
,
Affeld
,
K.
,
Kossatz
,
M.
,
Paschereit
,
C. O.
, and
Kertzscher
,
U.
,
2017
, “
Turbulence Measurements in an Axial Rotary Blood Pump With Laser Doppler Velocimetry
,”
Int. J. Artif. Organs
,
40
(
3
), pp.
109
117
.
19.
Pagani
,
F. D.
,
Miller
,
L. W.
,
Russell
,
S. D.
,
Aaronson
,
K. D.
,
John
,
R.
,
Boyle
,
A. J.
,
Conte
,
J. V.
,
Bogaev
,
R. C.
,
MacGillivray
,
T. E.
,
Naka
,
Y.
,
Mancini
,
D.
,
Massey
,
H. T.
,
Chen
,
L.
,
Klodell
,
C. T.
,
Aranda
,
J. M.
,
Moazami
,
N.
,
Ewald
,
G. A.
,
Farrar
,
D. J.
, and
Frazier
,
O. H.
,
2009
, “
Extended Mechanical Circulatory Support With a Continuous-Flow Rotary Left Ventricular Assist Device
,”
J. Am. Coll. Cardiol.
,
54
(
4
), pp.
312
321
.
20.
Slaughter
,
M. S.
,
Rogers
,
J. G.
,
Milano
,
C. A.
,
Russell
,
S. D.
,
Conte
,
J. V.
,
Feldman
,
D.
,
Sun
,
B.
,
Tatooles
,
A. J.
,
Delgado
,
R. M.
,
Long
,
J. W.
,
Wozniak
,
T. C.
,
Ghumman
,
W.
,
Farrar
,
D. J.
, and
Frazier
,
O. H.
,
2009
, “
Advanced Heart Failure Treated With Continuous-Flow Left Ventricular Assist Device
,”
N. Engl. J. Med.
,
361
(
23
), pp.
2241
2251
.
21.
Cooper
,
B. T.
,
Roszelle
,
B. N.
,
Long
,
T. C.
,
Deutsch
,
S.
, and
Manning
,
K. B.
,
2010
, “
The Influence of Operational Protocol on the Fluid Dynamics in the 12 CC Penn State Pulsatile Pediatric Ventricular Assist Device: The Effect of End-Diastolic Delay
,”
Artif. Organs
,
34
(
4
), pp.
1
23
.
22.
Long
,
T. C.
,
Pearson
,
J. J.
,
Hankinson
,
A. C.
,
Deutsch
,
S.
, and
Manning
,
K. B.
,
2012
, “
An In vivo Fluid Dynamic Study of Pediatric Cannulae: The Value of Animal Studies to Predict Human Flow
,”
ASME J. Biomech. Eng.
,
134
(
4
), p. 044501.
23.
Nanna
,
J. C.
,
Wivholm
,
J. A.
,
Deutsch
,
S.
, and
Manning
,
K. B.
,
2011
, “
Flow Field Study Comparing Design Iterations of a 50 CC Left Ventricular Assist Device
,”
ASAIO J.
,
57
(
5
), pp.
349
357
.
24.
Roszelle
,
B. N.
,
Cooper
,
B. T.
,
Long
,
T. C.
,
Deutsch
,
S.
, and
Manning
,
K. B.
,
2008
, “
The 12 CC Penn State Pulsatile Pediatric Ventricular Assist Device: Flow Field Observations at a Reduced Beat Rate With Application to Weaning
,”
ASAIO J.
,
54
(
3
), pp.
325
331
.
25.
Ziv
,
O.
,
Dizon
,
J.
,
Thosani
,
A.
,
Naka
,
Y.
,
Magnano
,
A. R.
, and
Garan
,
H.
,
2005
, “
Effects of Left Ventricular Assist Device Therapy on Ventricular Arrhythmias
,”
J. Am. Coll. Cardiol.
,
45
(
9
), pp.
1428
1434
.
26.
Hochareon
,
P.
,
Manning
,
K. B.
,
Fontaine
,
A. A.
,
Tarbell
,
J. M.
, and
Deutsch
,
S.
,
2004
, “
Correlation of In vivo Clot Deposition With the Flow Characteristics in the 50 Cc Penn State Artificial Heart: A Preliminary Study
,”
ASAIO J.
,
50
(
6
), pp.
537
542
.
27.
Kundu
,
P. K.
,
Cohen
,
I. M.
, and
Dowling
,
D. R.
,
2016
,
Fluid Mechanics
,
Elsevier
, New York.
28.
Baldwin
,
J. T.
,
Deutsch
,
S.
,
Petrie
,
H. L.
, and
Tarbell
,
J. M.
,
1993
, “
Determination of Principal Reynolds Stresses in Pulsatile Flows After Elliptical Filtering of Discrete Velocity Measurements
,”
ASME J. Biomech. Eng.
,
115
(
4A
), pp.
396
403
.
29.
Manning
,
K. B.
, and
Miller
,
G. E.
,
2002
, “
Flow Through an Outlet Cannula of a Rotary Ventricular Assist Device
,”
Artif. Organs
,
26
(
8
), pp.
714
723
.
30.
Prasad
,
A. K.
,
2000
, “
Particle Image Velocimetry
,”
Curr. Sci.
,
79
(
1
), pp.
51
60
.
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