A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock
Kazui et al. Journal of Cardiothoracic Surgery
A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock
Toshinobu Kazui 0 1 2 4 5
Phat L. Tran 0 1 4 6
Tia R. Pilikian 2
Katie M. Marsh 1 2 4
Raymond Runyan 3
John Konhilas 3
Richard Smith 6
Zain I. Khalpey 1 2 3 4 5 6 7
0 Equal contributors
1 College of Medicine - Tucson, University of Arizona , Tucson, AZ , USA
2 Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona , Tucson, AZ , USA
3 Department of Physiological Sciences, University of Arizona , Tucson, AZ , USA
4 College of Medicine - Tucson, University of Arizona , Tucson, AZ , USA
5 Division of Cardiohracic Surgery, Banner University Medical Center Tucson , 1501 N Campbell Ave., Rm 4302A, P.O. Box 245071, Tucson, AZ 85724-5071 , USA
6 Artificial Heart Program, Banner University Medical Center , Tucson, AZ , USA
7 Department of Biomedical Engineering, University of Arizona , Tucson, AZ , USA
Background: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy. Case presentation: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein. Conclusion: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.
Off-pump; Extracorporeal device; Left Ventricular Assist Device (LVAD); Refractory Cardiogenic Shock (RCS); Amniotic stem cell
Severe refractory cardiogenic shock (RCS) can be
defined as significant left or right ventricular dysfunction
resulting in sustained hypotension and hypoperfusion of
end-organs. Treatment for RCS would include one or
more modalities like pharmaco-agents (inotropes and
vasopressors), intra-aortic balloon pump (IABP),
revascularization in the case of myocardial infarction, and
ultimately mechanical circulatory support (MCS) system
to hemodynamically unload the heart and restore
circulation. One of such MCS system is the centrifugal
pumps like CentriMag (Thoratec Corp, Pleasanton, CA),
Rotaflow (MAQUET Cardiopulmonary AG, Hirrlingen,
Germany), or Sorin Revolution (Sorin Group USA, Inc.,
Arvada, CO). These temporary ventricular assist devices
(VAD) have been widely used as bridge-to-decision or
bridge-to-recovery in patients with refractory
cardiogenic shock [
]. However, cardiac recovery leading to
VAD explantation is still observed in a very small
Most of patients who require this therapy fall into
INTERMACS (Interagency Registry for Mechanically
Assisted Circulatory Support) profile1. Conventionally, the
temporary left VAD implantation has been performed
through median sternotomy with or without
cardiopulmonary bypass (CPB) support. These critically ill patients tend
to bleed more during and after surgery for pre-operative
liver dysfunction [
]. Especially for patient with previous
sternotomy, the dissection can take longer and bleed more.
Patients with VAD may also be benefited from stem
cell therapy (SCT), which has been shown to potentially
increase circulatory perfusion [
angiogenesis and reduction of fibrin formation after VAD
implantation , and improve ejection fraction (EF) [
More particularly, Nasseri et al. [
] looked at 10 patients
on long-term left ventricular assist device (LVAD)
concomitantly injected with bone marrow mononuclear cells.
They found one improved cardiac function resulting in
LVAD explantation, 2 deaths, and 7 others exhibited
increased perfusion. However, these case reports and series
are utilizing long-term LVAD support platform with
maximal inflammation induction from median sternotomy;
therefore creating an unfavorable environment for stem
cell engraftment and differentiation that may potentially
hinder cardiac recovery.
To recover the heart, a minimally invasive approach
with stem cell therapy was applied to reduce surgical
insult, avoiding CPB pump and median sternotomy. We
cannulated at the apex of the left ventricle and returned
through the right axillary artery with distal banding
technique to avoid hyperperfusion. We then administered a
bimodal delivery of amniotic stem cells with the intention of
initiating cellular myocardial recovery.
A 68-year-old female patient with past medical history
of, two previous coronary artery bypass grafts,
hypertension, chronic kidney disease, and diabetes mellitus,
presented to a local hospital with chest pain and
shortness of breath following an ST-elevation myocardial
infarction. The patient was placed on an IABP and
underwent a cardiac catheterization with the placement
of five stents in the left anterior descending artery and
saphenous vein graft. However she developed
postoperative cardiogenic shock and multi-organ hypoperfusion
despite her IABP and increased pressor requirements.
She was then transferred to our institution for possible
ventricular assist device placement.
Preoperative transesophageal echocardiography
(TEE) demonstrated EF of 10% with apical akinesis,
mild aortic insufficiency, moderate mitral and tricuspid
valve regurgitation. Right heart was functional
prompting for a CentriMag LVAD placement as
The patient was placed supine position. The position
of Left ventricular (LV) apex was confirmed by
transthoracic echocardiography. A 5 cm mini-thoracotomy
at 5th intercostal space was made. A pericardial well
was created and A Thoratec 34 Fr inflow cannula
(Thoratec Corp, Pleasanton, CA) was brought to the
field. The Thoratec cuff was sewn into the left
ventricular apex using plegetted 3–0 Ethibond sutures
followed by a running 3–0 Prolene suture. The right
axillary artery was exposed. Activated clotting time
guided heparin was confirmed to be more than 200 s.
An 8 mm Dacron graft was sewn into the axillary
artery in end-to-side fashion using a 4–0 Prolene
running suture. A 20 Fr EOPA cannula was passed
through the graft with the tip extending to the level of
the anastomosis. Silk ties were used to secure the
cannula to the graft. The distal axillary artery was banded
with a vessel loop. Banding prevented arterial and right
axillary artery distal from over perfusion and ensured
adequate cerebral perfusion. Remaining off-pump, the
34 Fr Thoratec inflow cannula was passed into the left
ventricle. The position was confirmed by TEE. The
cannula was secured to the cuff and was de-aired and
connected to the CentriMag device (Fig. 1). The
CentriMag was started and flow was established at 4.5 L/
min. Human allograft and liquid matrix was inserted
into the subclavian vein (2 times of 1cm3 of PalinGen
Kardia Flow, Amnio Technology, Phoenix, AZ, USA)
and into the anterior, lateral, and inferior walls of the
LV (1cm3 of PalinGen Kardia Flow each).
Her end organ function recovered during the
support. Transthoracic Echocardiography (TTE) was
conducted which showed LV recovery, EF 30% with
1.5 LPM of LVAD flow at post op day 13. At post op
day 20, fibrin clots developed in both the inflow and
outflow cannula connectors prompting for an urgent
decannulation at post op day 21. Upon off-pump
LVAD removal, a subsequent IABP was placed and
inotropic support was started in an effort to increase
coronary perfusion. A head CT scan showed evidence
of a small right sided ischemic cerebral infarct
possibly due to clots dislodgement from the support/
plumbing system or thrombotic occlusion of the right
brachiocephalic trunk, right common carotid, right
internal, and right vertebral arteries resulting in left
sided hemiplegia. Extubation, IABP removal, and
Fig. 1 Application of the Thoratec® CentriMag® LVAD with inflow
cannulation from the left ventricular apex, outflow cannulation via
8 mm Dacron graft into the right axillary artery, and arterial banding
distal to outflow
BiPAP administration was performed on post-explant
day three. The patient was discharge to rehabilitation
With regard to implantable LVAD, off pump placement
has been reported [
]. However, to our best knowledge,
this is the first dual therapy of using a temporary
offpump implantation of a CentriMag as a left ventricular
extracorporeal device with banding technique and
human amniotic stem cell. CentriMag LVAD placement
was performed in an off-pump fashion with left
minithoracotomy and adjusted distal arm flow by placing a
tourniquet. This is a viable short-term solution as bridge
to decision/recovery especially for patients with previous
sternotomy. Also, anastomosis of a graft to the right
axillary artery can further prevent complications relating
to direct axillary artery cannulation. This approach gave
us a flexibility to extubate and to mobilize the patient
while she was on the support. Avoiding the usage of
CPB and full sternotomy can also minimize
postoperative inflammation, preserve end organ function, and
potentially prevent RV dysfunction [
One of the potential disadvantages of this approach
was hyperperfusion of the right arm and right carotid
artery. We were able to avoid the latter complication by
tightening the axillary artery distal to the anastomosed
site via a tourniquet such that the right radial pressure
matched the left radial pressure upon stable support.
From the hemodynamic point of view, mechanically
unloading the heart has been shown to increase
survivability and promote differentiation of cardiac stem cells
injected in the myocardium of an infarcted animal heart
]; inhibit apoptotic mechanism and facilitated stem
cells engraftment in a mouse model [
]. It appears that
our minimally invasive off pump approach minimizes
sternotomy-induced myocardial inflammation, reduces
myocardial load, improves coronary perfusion such that
a favorable environment was created for amniotic stem
cell to engraft and resurrect the ailing heart. In fact, our
patient’s left ventricle EF improved from 10 to 30% by
postop day 13. This observed clinical improvement is
concurrent to bone marrow stem cell studies reported
by Gojo et al. [
] (EF improved from 6.4 to 40%) and
Miyagawa et al. [
] (EF improved from 22 to 32%).
Aside from safe to use, we think that direct stem cell
injection may provide myocardial functional recovery but
further study is highly warranted in the future.
The concomitant use of SCT and LVAD have been
previously reported by Dib et al. [
] and Pagani et al. [
However, they were using skeletal myoblasts, which is less
versatile than amniotic stem cells and long term LVAD,
which can inflict maximal surgical insults. Our
minimallyinvasive off-pump CentriMag LVAD placement has the
potential to achieve shorter recovery times and improve
clinical outcomes in profound RCS and previous cardiac
surgery patients. Finally, we further demonstrated that
dual therapy of LVAD and SCT is also feasible, safe, and
may be efficacious to LVAD explantation; thus moving
toward a more prescriptive/individualized medical therapy
for early and end stage heart failure patients.
CPB: CardioPulmonary Bypass; EF: Ejection fraction; IABP: Intra-aortic balloon
pump; LV: Left ventricle; LVAD: Left ventricular assist device; MCS: Mechanical
circulatory support; RCS: Refractory cardiogenic shock; SCT: Stem cell therapy;
TEE: TransEsophageal Echocardiography; TTE: TransThoracic
Echocardiography; VAD: Ventricular assist devices
The authors thank the OR and ICU staff.
Authors have no funding to disclose.
Availability of data and materials
Please contact author for data requests.
TK, PLT, KM, RS, and ZK were members of the surgical team. PLT, TRP, RR,
and JK were involved in drafting and critical revisions. All authors read and
approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
Written informed consent was obtained from the patient for publication of
this case report and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
1. Takayama H , Soni L , Kalesan B , Truby LK , Ota T , Cedola S , et al. Bridge-todecision therapy with a continuous-flow external ventricular assist device in refractory Cardiogenic shock of various causes . Circ Hear Fail . 2014 ; 7 : 799 - 806 .
2. Shuhaiber JH , Jenkins D , Berman M , Parameshwar J , Dhital K , Tsui S , et al. The Papworth experience with the Levitronix CentriMag ventricular assist device . J. Hear. Lung Transplant . 2008 ; 27 : 158 - 64 .
3. Mancini DM , Beniaminovitz A , Levin H , Catanese K , Flannery M , DiTullio M , et al. Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure . Circulation . 1998 ; 98 : 2383 - 9 .
4. Bhama JK , Kormos RL , Toyoda Y , Teuteberg JJ , McCurry KR , Siegenthaler MP. Clinical experience using the Levitronix CentriMag system for temporary right ventricular mechanical circulatory support . J. Hear. Lung Transplant . 2009 ; 28 : 971 - 6 .
5. Nasseri BA , Kukucka M , Dandel M , Knosalla C , Potapov E , Lehmkuhl HB , et al. Intramyocardial delivery of bone marrow mononuclear cells and mechanical assist device implantation in patients with end-stage cardiomyopathy . Cell Transplant . 2007 ; 16 : 941 - 9 .
6. Anastasiadis K , Antonitsis P , Argiriadou H , Koliakos G , Doumas A , Khayat A , et al. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion . J Transl Med . 2011 ; 9 : 12 .
7. Memon IA , Sawa Y , Miyagawa S , Taketani S , Matsuda H . Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy . J Thorac Cardiovasc Surg . 2005 ; 130 : 646 - 53 .
8. Gojo S , Kyo S , Nishimura S , Komiyama N , Kawai N , Bessho M , et al. Cardiac resurrection after bone-marrow-derived mononuclear cell transplantation during left ventricular assist device support . Ann Thorac Surg . 2007 ; 83 : 661 - 2 .
9. Sileshi B , Haglund NA , Davis ME , Tricarico NM , Stulak JM , Khalpey Z , et al. Inhospital outcomes of a minimally invasive off-pump left thoracotomy approach using a centrifugal continuous-flow left ventricular assist device . J Hear Lung Transplant . 2015 ; 34 : 107 - 12 .
10. Strueber M , Meyer AL , Feussner M , Ender J , Correia J-C , Mohr F-W. A minimally invasive off-pump implantation technique for continuous-flow left ventricular assist devices: early experience . J Heart Lung Transplant . 2014 ; 33 : 851 - 6 .
11. Kurazumi H , Li T , Takemoto Y , Suzuki R , Mikamo A . Haemodynamic unloading increases the survival and affects the differentiation of cardiac stem cells after implantation into an infarcted heart . Eur J Cardiothorac Surg . 2014 ; 45 : 976 - 82 .
12. Suzuki R , Li TS , Mikamo A , Takahashi M , Ohshima M , Kubo M , et al. The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment . J Thorac Cardiovasc Surg . 2007 ; 133 : 1051 - 8 .
13. Miyagawa S , Matsumiya G , Funatsu T , Yoshitatsu M , Sekiya N , Fukui S , et al. Combined autologous cellular cardiomyoplasty using skeletal myoblasts and bone marrow cells for human ischemic cardiomyopathy with left ventricular assist system implantation: report of a case . Surg Today . 2009 ; 39 : 133 - 6 .
14. Dib N , Michler RE , Pagani FD , Wright S , Kereiakes DJ , Lengerich R , et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up . Circulation . 2005 ; 112 : 1748 - 55 .
15. Pagani FD , DerSimonian H , Zawadzka A , Wetzel K , Edge ASB , Jacoby DB , et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: histological analysis of cell survival and differentiation . J Am Coll Cardiol . 2003 ; 41 : 879 - 88 .