Design Issues With Pediatric Mechanical Circulatory Support Systems

An adult or a pediatric patient with a failing heart may need medical device assistance to ensure life sustaining blood flow rate. Chronic mechanical circulatory support (MCS) systems supplements or replaces a patient’s failing native heart function. The primary system component is an implanted, blood pump that increases the pressure sufficient enough to overcome the downstream resistance thereby moving blood through the body.

The implanted blood pump is really just the start of the system—MCS systems contain many components include a wearable controller, AC and DC power adapters, battery packs with chargers, pump and cannulation tools for installation, clinical monitor, carry systems if the system is certified for ambulatory use, and safety training and associated material to educate all persons that may interact with the system. Figure 1 shows the components that a patient must competently operate. The controller is connected to the pump through a percutaneous driveline. Multiple phase drive waveforms are sent from the controller to operate the integrated pump motor. The controller also provides diagnostics including patient facing alerts and alarms based upon signal processing of the pump power consumption. The system has many safety and usability derived requirements, and as a complex medical device with frequent patient-led interactions, it requires a great deal of responsibility from patient and family for successful outcomes. The most common interaction is the exchange of depleted batteries with a fully charged battery.

Figure 1. The MCS system for advanced heart failure also called left ventricular assist device (LVAD). (Image courtesy of iStock/Graphic_BKK1979.)

Before diving into the unique challenges of designing for pediatric patients let us first cover the general technology used in MCS, and how this technology comes to market. Understanding the process may help understand the associated business and commercialization issues.

Blood pumps are typically a rotary design with a spinning impeller to transfer energy to the blood. A brushless DC motor is integrated within the pump and incorporates stator components within the pump casing and permanent rare earth magnets incorporated within the impeller. Blood pumps for chronic use require significant design work for the impeller suspension system to ensure “wearless” operation, dynamic stability, and durability for long term, fault tolerant operation. A pump fault may require a trip to the operating room for replacement with all of patient surgical risks. Positive displacement pumps are sometimes utilized to support patients but usually not chronically. These pumps work similar to a bicycle tire pump with one-way valves and a variable chamber that pushes blood downstream. This article will focus on rotary pumps.

Below is a simplistic overview of the MCS development process.

• Market identification and desire system “Intended Use”—this information forms the high-level system requirements such as duration and support level. These will be validated against clinical results during the regulatory approval process.
• Proof of concept development to provide sufficient probability that the overall program can be successful. Various designs can be evaluated which are then down-selected into the best candidate.
• Prototype development matures the leading proof of concept candidate into working prototypes that meet the required performance goals. MCS systems include a special focus on blood handling to avoid cellular inflammation and damage such as hemolysis and thrombosis which can cause embolization and may lead to mechanical pump failure. Manufacturing development begins in this phase to de-risk the for design for eventual commercialization. While prototyping typically implies a “quick and dirty” approach to building a few devices, in this application even prototypes destined for pre-clinical use will need to perform for months if not years to prove the concept has a future. Accelerated aging is common in electrical equipment but is not directly applicable to a mechanical pump system.
• Design development includes significant informal testing followed by formal verification and validation testing. This testing includes hydraulic performance, mechanical, biocompatibility, electrical safety, simulated clinical use, and human factors testing.
• Regulatory approval requires the objective evidence produced from testing and either a “substantial equivalence” analysis for an FDA 510(k) product or “investigational device exemption” (IDE) as part of a rigorous “premarket approval” (PMA) process. The PMA process is required for higher patient risk classes and often requires clinical trials to ensure patient safety and clinical effectiveness.
• Commercialization occurs post regulatory approval but requires rigorous company compliance efforts to ensure continuous clinical safety and effectiveness.

The process is complicated and requires significant funds to achieve commercial success and provide investors with sufficient and timely return on investments. This can be a significant hurdle for developing Pediatric MCS systems due to the much smaller market. The FDA recognizes this and has a Humanitarian Use Device classification for patients in need of therapy for populations not more than 8,000 individuals. There are additional design challenges for Pediatric systems creating additional hurdles.

The Federal Food and Drug Administration (FDA) regularly reports to Congress [1] on pediatric medical devices. FDA pediatric classifications are given below.

• Neonates—birth until one month of age.
• Infants—greater than one month of age until 2 years of age.
• Children—greater than 2 years of age until 12 years of age.
• Adolescents—greater than 12 years of age through 21 years of age.

FDA approved 59 pediatric medical devices in fiscal year 2021. Only 15 of these approvals were originally indicated for use within the pediatric population and the remaining 44 were originally indicated for use within adult population. For some therapies, pediatric patients just are not the same as adults. The currently approved left ventricular assist system, HeartMate 3, is excluded for patients less than 18 years old and patients with a body surface area less than 1.2 m2. Body surface area is commonly used metric for patient suitability for medical devices. Open literature [2] tabulates average body surface area as a function of age and is shown in Table 1. An average 10-year-old patient would be excluded from this treatment option based on BSA alone.

Pediatric heart failure patients requiring MCS support have additional requirements due to their physiology as well as different life experiences and Use Cases. For example, pediatric patients can have unique congenital etiologies such as univentricular physiology. Even for similar etiologies as adults, the differences in requirements can make an adult MCS system less than optimal for some or all pediatric classifications. Specific issues for a pediatric MCS system compared to an adult system include.

• Typically, the implanted blood pump is located within the thoracic cavity. The size of this space is a function of patient weight and BSA. Creating space for a pump requires careful thought to avoid interfering with other organs and internal structures. This becomes more difficult for an adult blood pump as the patient gets smaller and smaller. There may be a minimum ratio of thoracic volume versus pump volume necessitating smaller pumps to treat younger children.
• Inflow and outflow cannulation requirements are anatomically dictated. Congenital disease such as univentricular and Dextrocardia, heart orientation is reversed are unique to pediatric use. Heart size is typically about the size of the patient’s fist. Ventricular inflow canulation in a patient younger than adolescents may be ill suited if using an adult system. If an inflow cannula interferes with structures within the ventricle such as papillary muscles and valve chordae then other medical conditions could be introduced. Additionally, alignment of the inflow cannula with the tricuspid valve or tricuspid valve is required to ensure sufficient flow pathway to achieve the targeted flow rate and to minimize risk of inflow occlusion. Inflow occlusion produces suboptimal flow patterns and could lead to reduced support, hemolysis, and embolization.
• Circulatory support levels are a function of patient size and are reduced for pediatric use. Table 1 shows normal, average cardiac output for pediatrics. Adults typically require 4~6 L/min cardiac output. If the failing native heart is capable of pumping some blood, then the coupled MCS system can provide the rest. Having the native heart pump 25%~30% of the output then the aortic valve may periodically open to maintain some compliance. This means that a child of five years old needing 3 L/min then the MCS system needs to supply about 2 L/min, 60% less than the rate for adults.
• Rotary blood pumps are optimized during development for a specific support flow range and the performance is less than optimal outside of this range. Note that the pump flow rate is dependent upon the impeller rotational speed and the pressure difference between the downstream system pressure and the upstream blood supply. This behavior is shown in a pump head-flow performance (HQ) curve. When the heart contracts during systole or when it relaxes during diastole, the aortic pressure relative to the ventricular pressure difference varies causing pump flow rate to also vary. Lower pump flow rate for higher pressure differences and higher pump flow rates for lower pressure differences. An adult MCS with a mean output of 5 L/min may have flow of 2 L/min during diastole to 8 L/min during systole. The same MCS system in a child with a mean output of 2~3 L/min may have flow variation of 0–6 L/min. Pump flow rates near zero results in longer blood residence times increasing platelet activation and thrombosis risks.
• The Use Cases and human factors designs for pediatric use has significant differences. A pediatric patient does not provide primary system interaction where an adult patient is the primary system interaction. Additional trained care givers such as teachers are usually required for pediatrics patients. Back packs have been utilized in children utilizing MCS instead of waist bags and harness system common with adult systems. Children can be more active and accident prone compared to adults and could require more stringent shock loading and vibration testing. The use of a curly coil in the driveline may be beneficial to reduce loading on the exit site. Pulls on the percutaneous driveline exit site has been known to introduce infection risks. Swimming and bathing are prohibited with a percutaneous driveline which may be more detrimental to pediatrics patients compared to adults.
• Pediatric patient growth over time may present challenges to the inflow and outflow cannulation and driveline exit site selection. Optimal system installation may become suboptimal after a few years due to increased distances. Outflow cannulas that becomes too tight may become prone to kinking induced occlusion and the biological barrier at the driveline exit site may become compromised.

Even with these challenges, there is encouragement of using MCS therapy with pediatric patients. A retrospective study [3] of 142 pediatric patients showed 86% survived to transplantation, or recovery or have ongoing cases at 24 months after implantation. The study patients have a mean age of 13 years old and a mean body surface area of 1.4 m2. The study body surface area is reflective of a teenager according to Table 1 and is within the commercial indications of BSA greater than 1.2 m2. However, 28 patients were less than 11 years old with the youngest being only 3 years old!

What does the future hold for pediatric MCS systems? Today, current MCS technology works for some pediatric patients. There likely is a minimum BSA for adult MCS systems that can be safely used for children. If true, this necessitates new, smaller devices or modifications to the adult systems for sufficiently safe and effective therapy. It could be envisioned that an adult MCS system may be used in an ex-vivo system for infants and very young children. Also, an outflow cannula restriction may safely reduce the pump flow rate and reduce the flow variations during diastole and systole [4] Likely other approaches to enhance adult systems for this underserved pediatric patient population, such as different user interfaces or controls including integrating audio instructions or different external components such as smaller batteries. The alternative of new, specifically design pediatric MCS systems would likely be more effective than the current approach, but would require significant number of years to develop as well as significant funding.

References

1. Premarket Approval of Pediatric Uses of Devices, U.S. Food Drug Admin., Washington, DC, USA, 2021.
2. Nurse Key, Shock, Cardiac Arrest, and Resuscitation. Accessed: Jul. 6, 2024. [Online]. Available: https://nursekey.com/shock-cardiac-arrest-and-resuscitation/
3. M. Schweiger et al., “Use of intracorporeal durable LVAD support in children using HVAD or HeartMate 3—A EUROMACS analysis,” J. Cardiovascular Develop. Disease, vol. 10, no. 8, p. 351, Aug. 2023.
4. E. C. McGee et al., “Biventricular continuous flow VADs demonstrate diurnal flow variation and lead to end-organ recovery,” Ann. Thoracic Surg., vol. 92, no. 1, pp. e1–e3, Jul. 2011.