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Eur J Cardiothorac Surg 2008;34:1173-1178. doi:10.1016/j.ejcts.2008.06.042
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Pediatric heart support with a newly developed catheter based pulsatile 12F rotary blood pump: an animal study

Filip R. Regaa, Ingrid Vantichelena, Hilde Bollena, Veerle Leunensa, Guido Derjungb, Frank Kirchhofb, Eric Verbekenc, Bart P. Meynsa,*

a Department of Cardiac Surgery, University Hospital Leuven, Leuven, Belgium
b Abiomed Europe GmbH, Aachen, Germany
c Department of Pathology, University Hospital Leuven, Leuven, Belgium

Received 19 September 2007; received in revised form 17 June 2008; accepted 20 June 2008.

* Corresponding author. Address: University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Tel.: +32 16 344260; fax: +32 16 344616. (Email: bart.meyns{at}uzleuven.be).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Background: To evaluate mechanical and hematological compatibility of a pediatric, temporary left heart support system in a lamb model as a less traumatic alternative to the widely used ECMO. Methods: A small, pulsatile rotary blood pump (target flow 0.5 l/m at 80 mmHg pressure head at 120 pulses per min) was inserted in six lambs (15.1 ± 1 kg) via a left thoracotomy, through a purse string in the arcus aortae. With fluoroscopy the tip (=inflow) of the catheter was positioned in the outflow tract of the left ventricle. The outflow part was positioned immediately above the aortic valve. Animals were extubated at the end of the procedure. Mechanical and hematological parameters were followed for 14 days. Results: Five animals survived a 2-week follow-up. One animal died because of empyema on day 6. Flow maintained stable (0.8 ± 0.2 l/m) in all animals during the evaluation period. Free hemoglobin as a parameter of hemolysis and hematocrit remained also stable. Necropsy revealed minimal fibrous reaction on one aortic valve leaflet in one animal and small hematoma formation in three. All animals showed mild signs of endothelial damage on the aortic arch at the level of the motor housing. One animal showed signs of old kidney infarction suggesting possible embolization during placement. Conclusion: This newly developed, catheter based, pediatric heart support system generates a stable flow for 14 days without compromising hematological stability and with acceptable tissue damage due to positioning of the catheter.

Key Words: Congenital heart disease: Heart failure • Assist device


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Mechanical circulatory support in the treatment of congenital heart disease becomes more and more important; however, the pediatric population has not received the same attention in terms of product development. Despite the rapid expansion of left ventricular assist device (LVAD) support for adults, extra corporeal membrane oxygenation (ECMO) and centrifugal pump based assist devices remain the most common form of mechanical support for pediatric cardiac patients [1].

Children with heart failure of various etiologies may require temporary use of assist devices as last resource therapy, particularly in the perioperative period of congenital or acquired cardiac defects. The aims for application of mechanical support are three-fold: (1) maintain systemic circulation, (2) avoid multiple organ failure and (3) bridge to myocardial recovery or to transplantation. The number of cardiac ECMO support cases following data from the International Extracorporeal Life Support Registry for children under 1 year was 3922, mostly for congenital heart disease (n = 3324 or 84.7%) [2].

Not only the small number of affected pediatric patients but also the anatomical and physiological limitations make it difficult for manufacturers to develop devices for this subset of patients [3]. The rotary blood pump is attractive because of its simplicity and small size. The objective of the Impella pediatric development is to provide the smallest cardiac patients (3–10 kg) with temporary direct or peripherally inserted left heart support for up to 14 days as a less traumatic alternative to ECMO. The goal of this study was to evaluate mechanical and hematological compatibility of the pediatric Impella as temporary left heart support system in a lamb model.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 Appendix A
 References
 
The purpose of this study was to evaluate mechanical and hematological compatibility of a pediatric, temporary left heart support system in a lamb model. Therefore lambs were selected. All animals received humane care in compliance with the guide for the care and use of laboratory animals, published by the national institutes of health.

2.1 The newly developed rotary pump
Based on the Impella LP2.5 (Abiomed, Aachen, Germany), now used clinically for temporary heart support with flows up to 2.5 l/min for prophylactic use in high risk interventions and for transient hemodynamically compromised patients, Abiomed introduced a percutaneous catheter based 12F device (Fig. 1 ) [4–8]. The LP2.5 was geometrically adopted to operate in our smallest patients (3–10 kg) with target flows around 0.5 l/min and a pulsatile flow pattern for improved end organ perfusion. Due to the minimal mass of the motor and rotor assembly along with abundant torque reserves, the rotary pump speed can be modulated with amplitudes of 30,000 rpm in 200 ms intervals with virtually no additional power required. This leads to a target flow of 0.5 l/min at a 80 mmHg pressure head at 120 pulses per min. Higher flows up to 1.5 l/min are easily achievable by an extension of the high-speed interval. Consequently, this rotary pump generates a pulsatile flow at a sincerely reduced risk of suction in small hearts.


Figure 1
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  		Fig. 1. Design of Impella pediatric.

 
In addition, the outer diameter of the transvalvularly placed inflow cannula has been further reduced to 9F in order to avoid any valve obstruction and the length has been adopted to a ventricular cavity similar in size to a plumb (<15 cc). Furthermore, the cannula has been precurved to obtain a second degree of freedom for placement of the inflow cage within the ventricular cavity rather than adjacent to any cardiac structure by mere pump and respective cannula rotation.

2.2 Animal preparation
Six lambs (15.1 ± 1 kg) were premedicated with ketamine (15 mg/kg intramuscularly). After the animal was placed in the right lateral decubitus, a peripheral venous line was placed in the left lower limb. Na-penicilline (40,000 UI/kg) and gentamycin (6.6 mg/kg) were administered intravenously for antibiotic prophylaxis. Anesthesia was induced by mask delivery of an isoflurene–oxygen mixture. The animals were intubated and ventilated with a Dräger Julian ventilator (Dräger, Lübeck, Germany). Anesthesia was maintained with 1.5–2.5% isoflurane. All ventilation parameters were adjusted to keep the blood gas values within the normal range. Surface electrocardiographic leads were applied and a fluid filled pressure catheter was placed in the left ear artery to enable monitoring of the vital parameters.

A left thoracotomy was performed through the fourth inter-costal space. Heparin (300 U/kg) was administered and further maintained to keep activated clotting time above 250 s. The pediatric Impella was inserted through a purse string in the ascending aorta. Under fluoroscopic guidance the tip (=inflow) of the catheter was positioned in the outflow tract of the left ventricle (Fig. 2 ). The outflow part was positioned immediately above the aortic valve. Blood is directly drained from the left ventricle to be expelled in the ascending aorta.


Figure 2
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  		Fig. 2. Fluoroscopic view in right lateral decubitus.

 
With an intra-thoracic loop the drive line of the pump was tunneled subcutaneously and fixed at the back of the animal. Animals were woken at the end of the procedure. Activated clotting time was kept between 100 and 180 s.

2.3 Experimental protocol
Performance of the pediatric Impella was continuously recorded (motor current (mA), speed (rpm), flow (l/min), pressure head (mmHg)) using specially designed hard and software for this purpose (Abiomed, Aachen, Germany).

Baseline measurements included blood sampling for measurement of plasma free hemoglobin and hemoglobin. Further blood sampling was performed on day 1, 3, 5, 8, 11 and 13 days after implantation.

Fourteen days after implantation a necropsy was performed with special attention to cannula positioning, possible damage at the level of the aortic valve and erosion of the catheter mounted pump. All necropsies were performed by one experienced pathologist (EV).

2.4 Data analysis
Results are represented as mean ± SD and were calculated using MS Excel 2003 and STATISTICA 7.1 (Statsoft Inc., Tulsa, OK, USA). Error bars in figures denote mean ± standard deviation.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 Appendix A
 References
 
Five animals survived a 2-week follow-up. One animal died because of massive empyema on day 6.

3.1 Hemodynamic data
Pump data and pump hemodynamics (pump current: Fig. 3A – placement signal: Fig. 3B – speed: Fig. 3C – flow: Fig. 3D) are depicted in Fig. 3. Flow maintained stable (0.8 ± 0.2 l/min) in all animals during the evaluation period (Fig. 3D).


Figure 3
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  		Fig. 3. Motor pump action during the 2-week follow-up. Error bars denote mean ± standard deviation. (A) Motor current; (B) placement signal; (C) speed; (D) flow.

 
3.2 Blood sampling data
Blood sampling data are depicted in Fig. 4 (Fig. 4A) and plasma free hemoglobin (Fig. 4B) stayed stable in all animals’ hemoglobin for the duration of the Impella run reflecting the absence of hemolysis.


Figure 4
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  		Fig. 4. Blood sampling results: (A) hemoglobin; (B) free plasma hemoglobin.

 
3.3 Necropsy of the thoracic cage and abdomen
Necropsy findings are represented in Table 1 and Fig. 5 . Necropsy revealed polypoid tissue on one aortic valve leaflet in one animal, histologically compatible with infectious endocarditis (Fig. 5A) and small hematoma formation in three animals (Fig. 5C). All animals showed mild signs of endothelial damage on the aortic arch at the level of the motor housing (Fig. 5B). One animal showed signs of old kidney infarction suggesting possible embolization during placement. In one animal a kinked catheter was retrieved during autopsy (Fig. 5D).


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  		Table 1 Macroscopic findings during necroscopy in all animals
 

Figure 5
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  		Fig. 5. Macroscopic inspection during necroscopy in all animals. (A) Polyp on the non coronary cusp of the aortic valve, histologically compatible with infectious endocarditis; (B) imprint of motorhousing on ascending aorta wall; (C) hematoma on right coronary cusp of aortic valve; (D) kinked catheter proximal from motorhousing.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
Appendix A
 References
 
In a lamb model we evaluated the mechanical and hematological compatibility of a newly developed, catheter mounted, micro-axial flow pump, designed to be used for temporary heart support in neonates and babies from 3 to 10 kg. Besides one, all animals survived a 2-week follow-up with well functioning pumps. No hemolysis was observed. Minimal device related damage was found during necroscopy.

Mechanical unloading of the myocardium during ischemia and reperfusion has been shown to reduce left ventricular pressure work and myocardial oxygen consumption [7]. Support by micro-axial blood pumps has proven to reduce myocardial oxygen consumption during ischemia and reperfusion, leading to a reduction of infarct size [9]. In the same study these authors found that the degree of reduction in infarct size correlated with the degree of support, reflecting the possible benefit of full support with the pediatric Impella in post-cardiotomy heart failure in neonates, compared to partial support using ECMO.

In our setting the pump was positioned via thoracotomy, enabling the surgeon to guide the catheter and ensure correct positioning. A purse string was placed on the ascending aorta through which the catheter was brought in place. In the clinical setting, using the adult Impella we first sew an 8 mm Dacron graft end-to-site on the ascending aorta through which the device is placed, positioned and fixed. This technique allows optimal manipulation without damaging the aorta which can be very calcified or thin walled. In our lamb model direct introduction in the aorta worked well. In comparison with placement of central ECMO cannulas in neonates and young children we are convinced that direct placement of the pediatric Impella into the aorta is feasible.

Concerning damage on the aortic valve leaflets we found two types of lesions: granulation tissue and minimal signs of contact erosion. The pediatric Impella is developed to be used as short-term bridge to recovery, meaning no longer then 7 days. Since in 4/6 experiments only minimal erosions were noted after 14 days of implantation we can assume no major or definitive impact is expected. As we only looked at mechanical and hematological compatibility of the pediatric Impella, impact on aortic valve cusps has to be examined in long-term safety experiments.

The pediatric Impella can be used for two indications. In post-cardiotomy heart failure in neonates with congenital heart disease, requiring temporary left heart support, direct positioning of the pump via sternotomy can be performed as in our experimental setting. The advantage of this pump over ECMO in these situations will than be: (1) small device, (2) low foreign body surface contact, (3) lesser need for anti-coagulation, and (4) lower rate of bleeding complications.

If no sternotomy is required an approach via the carotid artery can be considered. We use this access in neonates to insert the arterial outflow cannula of the ECMO system with a caliber of 10F when needed. The current developed 12F pediatric cannula may be too big only for our smallest patients with very low birth weights. This counts not only for the diameter but also for the length of the device. To illustrate this Fig. 6 shows the relation between the pediatric Impella and the heart of a neonate weighing 3.7 kg operated for ventricular septum defect.


Figure 6
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  		Fig. 6. Relation between pediatric Impella and the heart of a neonate weighing 3.7 kg operated for ventricular septum defect.

 
A unique feature of this device is its possibility to generate a pulsatile flow up to 120 ‘beats’ per min. However, little evidence exists on the benefit of running a pulsatile flow with left ventricular support devices [10,11]. To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, Orime and co-workers found, in a pig model, that liver tissue flow, renal cortex flow and stomach mucous flow was significantly higher in the group when a pulsatile pump was used [12].

The actual reason for this pediatric Impella to generate a pulsatile flow is the fact that it was a solution to the specific problem of modulating the high flow in combination with a low afterload in the pediatric population. By varying pump speed from 25,000 to 55,000 rpm, lower flows to 0.5 l/min could be generated. By increasing the high-speed interval higher flows are possible. A secondary, though not proven, advantage of this type of pulsatility is the fact that suction can be avoided in these small, neonatal ventricles and that there is a decreased risk of clotting.

Based on the findings of this study, further research will be focused on optimizing the kinking resistance of the catheter, the development of an optimal implantation technique and anatomical cadaver fit studies to adopt if needed the size of the catheter and pump to fit in our smallest patients.

In conclusion this newly developed, catheter based, pediatric heart support system generates a stable flow for 14 days without compromising hematological stability and with acceptable tissue damage due to positioning of the catheter.


   Appendix A
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
References
 
Conference discussion

Dr J. Horisberger (Lausanne, Switzerland): It's quite an interesting project with the Impella pump. Obviously you have done this study on 15 kg lambs and you’re talking about putting it in a 3 kg child. You would expect to see more damage in such a small child. A 12 French catheter is fairly large.

Dr Rega: Indeed this is quite large and the engineers are working on a smaller device. We believe we can use our device safely in neonates from 5 kg. So far we have no arguments to assume that there is going to be much more damage than seen here after a 14-day interval. As a bridge to recovery, you are not going to use this device so long. In most cases post-cardiotomy heart failure is resolved after 1 week.

Dr Horisberger: Because with the adult Impella, in fact, it's 7 days maximum.

Dr Rega: Yes, indeed.


   Acknowledgments
 
The authors appreciated the help and continuous support of Thorsten Siess (Abiomed, Aachen).


   Footnotes
 
{star} Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.

{star}{star} Disclosure statement: Bart Meyns is a consultant for Abiomed.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 

  1. Duncan BW. Mechanical circulatory support for infants and children with cardiac disease. Ann Thorac Surg 2002;73:1670-1677.[Abstract/Free Full Text]
  2. Conrad SA, Rycus PT, Dalton H. Extracorporeal Life Support Registry Report 2004. ASAIO J 2005;51:4-10.[CrossRef][Medline]
  3. Duncan BW. Pediatric mechanical circulatory support: a new golden era?. Artif Organs 2005;29:925-926.[CrossRef][Medline]
  4. Henriques JP, Remmelink M, Baan Jr. J, Van Der Schaaf RJ, Vis MM, Koch KT, Scholten EW, De Mol BA, Tijssen JG, Piek JJ, De Winter RJ. Safety and feasibility of elective high-risk percutaneous coronary intervention procedures with left ventricular support of the Impella Recover LP 2.5. Am J Cardiol 2006;97:990-992.[CrossRef][Medline]
  5. Siess T, Nix C, Menzler F. From a lab type to a product: a retrospective view on Impella's assist technology. Artif Organs 2001;25:414-421.[CrossRef][Medline]
  6. Valgimigli M, Steendijk P, Sianos G, Onderwater E, Serruys PW. Left ventricular unloading and concomitant total cardiac output increase by the use of percutaneous Impella Recover LP 2.5 assist device during high-risk coronary intervention. Catheter Cardiovasc Interv 2005;65:263-267.[CrossRef][Medline]
  7. Dennis C, Hall D, Moreno J, Senning A. Reduction of the oxygen utilization of the heart by left heart bypass. Circ Res 1962;10:298-305.[Abstract/Free Full Text]
  8. Dens J, Meyns B, Hilgers R, Maessend J, Van Ommen V, Gerckens U, Grube E. First experience with the Impella Recover LP 2.5 micro axial pump in patients with cardiogenic shock or undergoing high-risk. Euro Interv 2006;2:84-90.
  9. Meyns B, Stolinski J, Leunens V, Verbeken E, Flameng W. Left ventricular support by catheter-mounted axial flow pump reduces infarct size. J Am Coll Cardiol 2003;41:1087-1095.[Abstract/Free Full Text]
  10. Feller ED, Sorensen EN, Haddad M, Pierson III RN, Johnson FL, Brown JM, Griffith BP. Clinical outcomes are similar in pulsatile and nonpulsatile left ventricular assist device recipients. Ann Thorac Surg 2007;83:1082-1088.[Abstract/Free Full Text]
  11. Klotz S, Deng MC, Stypmann J, Roetker J, Wilhelm MJ, Hammel D, Scheld HH, Schmid C. Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support. Ann Thorac Surg 2004;77:143-149.[Abstract/Free Full Text]
  12. Orime Y, Shiono M, Nakata K, Hata M, Sezai A, Yamada H, Iida M, Kashiwazaki S, Nemoto M, Kinoshita J, Kojima T, Saito T, Sezai Y. The role of pulsatility in end-organ microcirculation after cardiogenic shock. ASAIO J 1996;42:M724-M729.[Medline]




This Article
Right arrow Abstract Freely available
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Right arrow Email this article to a friend
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Right arrow Author home page(s):
Filip R. Rega
Bart P. Meyns
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Right arrow Articles by Rega, F. R.
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Right arrow Articles by Rega, F. R.
Right arrow Articles by Meyns, B. P.
Related Collections
Right arrow Mechanical Circulatory Assistance

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