History of MicroMed and the DeBakey VAD®
In 1984 David Saucier, a NASA Johnson Space Center engineer, underwent a successful heart transplant under the care of Dr. George P. Noon and Dr. Michael E. DeBakey. It was during Mr. Saucier’s recovery that he had discussions with Drs. Noon and DeBakey in which they expressed their desire to develop a long-term ventricular assist device. Dr. DeBakey already had decades of experience in developing blood pumps, however, Mr. Saucier believed that if he could arrange for NASA to work with Drs. Noon and DeBakey, then they would finally be able to bring to fruition a long term, safe and effective ventricular assist device.

The first formal meeting between the teams at Baylor College of Medicine and Johnson Space Center (JSC) occurred in 1988 when the Baylor team traveled to JSC to explore a cooperative effort to develop a new blood pump.  As a result of this meeting, and the desire for this joint development effort to succeed, a Memorandum of Understanding was signed that formalized the joint project and defined NASA’s official participation.

One of the first questions that the NASA engineers asked was if the pump had to be pulsatile? Or if it could be made as a rotary pump since NASA engineers had considerable expertise at designing and building continuous-flow pumps.  Although the long term physiological effects of a continuous-flow blood pump were not known, it was believed that only a rotary blood pump would be able to achieve the desired small size and 5-plus year durability that was necessary.

Once it was decided that a continuous-flow pump would be designed and fabricated, traditional pump design methods were utilized.  The techniques and formulas from A. J. Stepanoff’s Centrifugal and Axial Flow Pumps [1] were used.  The first step in the design process was to address the performance requirements of the blood pump set forth by Drs. Noon and DeBakey as 5 liters per minute (lpm) against a pressure of 100 millimeters of mercury (mmHg).  The second important step was selecting an operating speed for the pump.  As the speed of a pump is increased, the size of the pump is decreased for a given set of performance criteria.  Additionally, the type of impeller design is generally set forth by a ratio of speed, flow and pressure, known as the specific speed [2].  High specific speed pumps use an axial impeller design, low specific speed pumps use a centrifugal impeller design, and specific speed pumps in between axial flow and centrifugal flow use a Francis type or mixed flow impeller design.

In 1995, through a relationship with Dr.DeBakey’s associates, Travis Baugh and Dallas Anderson formed MicroMed Technology, LLC with the intention of licensing and commercializing this technology from NASA.  After an arduous and nearly year long path, Dallas and Travis, with the help of Dr. DeBakey and the Technology Transfer Office of Johnson Space Center, obtained an exclusive license in 1996 and MicroMed Technology became incorporated.  This is also the year that David Saucier passed away and, unfortunately, he was never able to see the realization of the dream he shared with Drs. Noon and DeBakey.   

The focus of MicroMed was to A) transform the ex-vivo components into an implantable VAD; B) demonstrate the long term reliability of the pump; C) develop all the external electronics and ancillary equipment; D) Perform all necessary pre-clinical (in-vitro and in-vivo) testing necessary and bring the technology to the patients who desperately need such a device.  The first step to achieving any, and all, of these goals was contingent on raising enough capital to accelerate the development.  Once this initial financing was in place, a parallel development process was initiated and individual tasks were outsourced to respective industry experts.

To address the conversion of the ex-vivo two week pump, into a long term implantable pump, all components required materials and manufacturing process that would survive in the hostile environment of the human body.  Especially challenging were the encapsulation of the magnets in the impeller and the development of the percutaneous cable.  Early in the development stage of this project, while still at NASA, miniature titanium cans were produced to encapsulate each magnet.  It was then planned that an electron beam would weld a cap onto the top of the titanium can.  This ultimately did not work since the rare earth magnets were strong enough to deflect the electron beam and the cans could not be welded.  MicroMed devised a method to encapsulate the magnets directly into the titanium blades and laser weld titanium caps on top of the magnets.  In developing the percutaneous cable, the lessons learned from the space industry as well as implantable pacemaker leads were directly applied to the VAD cable.  The cable that was designed provided tremendous strength, fatigue resistance, acceptable electrical resistance, and small diameter.  It is this size and flexibility of the percutaneous cable that offered the greatest potential for reduced exit site infection. 

 

In hindsight, it is daunting to realize how much work was necessary after we believed the pump design was essentially finished.  A fault tolerant controller needed to be developed that conformed to seemingly impossible contradictory requirements of electromagnetic immunity, leakage current and defibrillation proof.  The early prototype controller work by Richard Boseman of Johnson Space Center and George Damm of Baylor college of medicine worked well for the in vitro and ex-vivo experiments, but would have to be essentially re-designed from scratch in order to meet the requirements for a FDA regulated Class III implantable device.  MicroMed was fortunate enough to contract the services of Hi-tronics Designs, Inc., a New Jersey based company that had considerable experience with electrically powered, implantable devices, and Transonic Systems, Inc., a New York based company that developed and manufactured transit time ultrasound flow probes.  The result was the first clinical, patient carried, VAD controller with a built-in two channel flow meter, “smart battery” technology, and an alpha-numeric liquid crystal display of real time pump parameters and alarm conditions. To compliment this sophisticated controller, a Clinical Data Acquisition System (CDAS) was developed which could display real time waveforms of pump flow, pump current and arterial pressure (through an external pressure probe).  The CDAS automatically stores the pump parameters once per minute providing a valuable history of the pump’s performance and in some cases of the patient’s condition as well.  An interesting sidebar is that the development of the motor and electronics for the VAD was greatly accelerated by the advances in the laptop industry.  The motor controller that is utilized was primarily used as a motor controller for hard disk drives.  The magnet development was also pushed by the hard disk drive industry as disk drive motors pushed to become smaller and faster.  Even the portable, rechargeable battery industry was advanced by the laptop industry and these same batteries became the first batteries used in the VAD system.   

With the system components nearing completion, one of the most rigorous obstacles lay ahead: verification and validation testing to meet the regulatory requirements.  MicroMed made the decision to begin the clinical study in Europe as the regulatory requirements and time-frame were thought to be faster than in the U.S.  One reason the author believes the European path is “easier” is that there are well-structured testing and compliance requirements.  If one successfully passes these requirements, then one could assume the device achieved a minimum level of safety, and a clinical study could commence.  Some examples of standardized tests include:  biocompatibility of the materials used in the construction of the device; sterilization validation; immunity to electrical and electromagnetic interference; minimum levels of electrical leakage, both from the device to the patient if the patient is grounded, and from the patient to the devices if the patient is exposed to electric shock (the device must not allow electrical current to pass through their myocardium to a device that is grounded).  In addition to these standardized tests, a successful pre-clinical animal study using clinical quality equipment was necessary.  All of these verification tests, and the manufacturing of the devices, fell under the umbrella of a Quality System that is accountable for designing, testing and manufacturing implantable devices.  The amount of process control, traceability and record keeping can never be underestimated for a Class III implanted device.  MicroMed was successful in building the infrastructure and moving the technology to the clinical arena in less than three years, without a single regulatory non-conformity.    

In November of 1998, the first implants of the DeBakey VAD were performed at the Deutsches Herzzentrum Berlin, Berlin Germany. Dr. Roland Hetzer performed the implant with the assistance of Dr. DeBakey and Dr. Noon.  These landmark cases were the first ever of implantable rotary blood pumps to support long-term bridge to transplant patients.  The lessons learned from these first two cases were invaluable in understanding continuous-flow devices and moving this new technology forward [16, 17,18,19,20].  The third and fourth patients were implanted at the Allgemeines Kranken Haus Wien (AKH) in Vienna, Austria under the hands of Drs. Ernst Wolner and Georg Wieselthaler, again with assistance of Dr. DeBakey and Dr. Noon.  These two patients were the first to survive successful transplants after 74 and 115 days respectively [21, 22].  In 1999, the DeBakey VAD was inducted into the U.S. Space Foundation’s Space Technology Hall of Fame.  In 2001, the CE Mark, Europe’s equivalent to a PMA approval, was obtained.  The clinical trial of the DeBakey VAD in the U.S. was started in June, 2000, at Methodist Hospital, Houston, with a patient implanted under the hands of Dr. Noon and of Dr. DeBakey. Upon successful completion of the feasibility trial, the FDA granted approval of a pivotal trial for the bridge to transplant indication in 2001 and later the pivotal trial for the destination therapy indication in 2003.  More than 445 patients have been implanted with the DeBakey VAD. 

One of the most compelling features of the DeBakey VAD is the size.  For this reason, Dr. Anthony Chang of Texas Children’s Hospital approached Dr. DeBakey with the desire to make the DeBakey VAD available to the pediatric population that had no other options for mechanical circulatory support.  With this new mission, MicroMed modified the adult version of the DeBakey VAD to provide a better anatomical fitting in the pediatric chest without modifying the pump’s core components.  As a result, MicroMed received a Humanitarian Device Exemption (HDE) in 2004 for the DeBakey VAD Child and the first patient implanted with this device was at Texas Children’s Hospital in a six year old girl [23]. As with the first adult experiences, many lessons were learned in this uncharted territory of implanted rotary blood pumps in children and, as of this writing, the DeBakey VAD® Child has been implanted in many US pediatric patients.

In conclusion, a special thanks is necessary for Dr. Noon and Dr. DeBakey for their steadfast support and guidance, which was the catalyst to bring this technology to clinical use.  Special thanks also go to all who participated in the development of the DeBakey VAD.  It would be impossible to list all the contributors from NASA, Baylor College of Medicine, the Artificial Heart Lab in Utah, Texas A&M University, MicroMed Technology, Inc., and the numerous surgeons and patients who braved this new frontier in mechanical circulatory support.

References

1. Stepanoff A.J., PhD. Melville Medalist, A.S.M.E. Centrifugal and Axial Flow Pumps. 2nd Edition.1970. Ingersoll-Rand Company

2. Karassik IJ, Krutzsch WC, Fraser WH, Messina JP. Pump Handbook. 1976.  McGraw-Hill Book Company.

3. Potapov EV, Loebe M, Nasseri BA, Sinawski H, Koster A, Kuppe H, Noon GP, DeBakey ME, Hetzer R.  Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device. Circulation. 2000;102(suppl III):III-183-III-187.

4. Koster A, Loebe M, Hansen R, Potapov EV, Noon GP, Kuppe H, Hetzer R.  Alterations in coagulation after implantation of a pulsatile Novacor LVAD and the axial flow MicroMed DeBakey LVAD®.  Ann Thorac Surg. 2000;70:533-7.

5.  Loebe M, Koster A, Sanger S, Potapov E, Kuppe H, Noon GP, Hetzer R.  Inflammatory response after implantation of a left ventricular assist device: comparison between the axial flow MicroMed DeBakey VAD® and the pulsatile Novacor device.   ASAIO J. 2001;47:272-274.

6. Potapov EV, Koster A, Loebe M, Hennig E, Fischer T, Sodian R, Hetzer R.  The MicroMed DeBakey VAD®-Part I:  The pump and the blood flow. Extra Corpor Technol 2003 Dec;35(4):274-83.

7. Fischer T, Koster A, Potapov EV, Gutsch E, Loebe M, Hetzer R, Kuppe H.  The MicroMed DeBakey VAD®-Part II: Impact on the hemostatic systems.  J Extra Corpor Technol 2003 Dec;35(4):284-286.

8. Wieselthaler GM, Schima H, Hiesmayer M, Pacher R, Laufer G, Noon GP, DeBakey ME, Wolner E.  First clinical experience with the DeBakey VAD® continuous-axial-flow pump for bridge to transplantation.  Circulation. 2000;101:356-359.

9. Wieselthaler GM, Schima H, Dworschak M, Quittan M, Nuhr M, Czerny M, Seebacher G, Huber L, Grimm M, Wolner E.   First experiences with outpatient care of patients with implanted axial flow pumps. Artif Organs. 2001;25(5):331-335.

10. Morales DLS, DiBardino D, McKenzie ED, Heinle JS, Chang AC, Loebe M, Noon GP, DeBakey ME, Fraser CD.  Lessons Learned from the First Application of the DeBakey VAD® Child:  An Intracorporeal Ventricular Assist Device for Children.  The Journal of Heart and Lung Transplantation.  Vol 24, Issue 3, March 2005, pp 331 – 337.