medical devices Archives

Children’s National awarded nearly $7.5 million by FDA to lead pediatric device innovation consortium

November 2, 2023

Children’s National Hospital was awarded nearly $7.5 million in a five-year grant to continue its leadership of an FDA-funded pediatric device consortium. Building upon a decade of previous consortium leadership, the new consortium is Alliance for Pediatric Device Innovation (APDI) and features a new and expanded roster of partners that reflects its added focus on providing pediatric innovators with expert support on evidence generation, including the use of real-world evidence (RWE), for pediatric device development.

Collaborating for success

With the goal of helping more pediatric medical devices complete the journey to commercialization, APDI is led by Children’s National, with Kolaleh Eskandanian, Ph.D., M.B.A., vice president and chief innovation officer, serving as program director and principal investigator, and Julia Finkel, M.D., pediatric anesthesiologist and director of Pain Medicine Research and Development in the Sheikh Zayed Institute for Pediatric Surgical Innovation, serving as principal investigator.

Consortium members include Johns Hopkins University, CIMIT at Mass General Brigham, Tufts Medical Center, Medstar Health Research Institute and MedTech Color. Publicly traded OrthoPediatrics Corp., which exclusively focuses on advancing pediatric orthopedics, is serving as APDI’s strategic advisor and role model for device innovators whose primary focus is children.

Why we’re excited

Consortium initiatives got underway quickly with the announcement of a special MedTech Color edition of the “Make Your Medical Device Pitch for Kids!”^™competition that focuses on African American and Hispanic innovators. Interested innovators can find details and apply at MedTech Color Pitch Competition. The competition was announced at the recent MedTech Color networking breakfast on Oct. 10,2023 at The MedTech Conference powered by AdvaMed.

“We all benefit from greater equity and inclusion among pediatric MedTech founders, decision-makers, investigators and developers in more effectively addressing the needs of the entire pediatric population,” said Eskandanian. “We need the expertise and insights of innovators from diverse backgrounds, and we want to provide these talented individuals with more opportunities to present their work and share their perspectives on pediatric device development.”

Additional details

APDI is one of five FDA-funded consortia created to provide a platform of services, expertise and funding to help pediatric innovators bring medical devices to the market that specifically address the needs of children.

NIH awards $1.8 million to trial pacemaker delivery system for children

November 16, 2022

The PeriPath access port makes it possible for pacing and defibrillating leads to be placed in the smallest children through holes the size of a straw.

A $1.8 million Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH) is funding the first clinical trial of a novel device called PeriPath. The device makes it possible for pacing and defibrillating leads (or wires) to be placed in the smallest children through holes the size of a straw, eliminating thoracotomy or sternotomy procedures for children who are too small for transvenous implantation.

Even the tiniest pacemakers and defibrillators on the market today aren’t small enough for infants and young children with heart rhythm abnormalities. Innovating smaller devices, including adapting current technology like the Medtronic Micra for pediatric use, is a good start but won’t be enough to eliminate some of the challenges for these patients. When a newborn or young child needs any pacemaker or defibrillator, they face open chest surgery. Their arteries and veins are just too small for even the smallest size transvenous pacemaker catheter.

The research goal

Charles Berul, M.D., division chief of Cardiology and co-director of the Children’s National Heart Institute, partnered with engineers in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital to develop and test a first-of-its-kind minimally invasive pericardial access tool. The tool allows doctors to place pacing and defibrillation leads to the epicardial surface of the heart under direct visualization from an endoscope.

The team hypothesizes that this tool will allow for pacing and defibrillation therapy to be delivered through a single small port inserted through the skin that is about the size of a drinking straw.

Why it matters: Less pain, shorter and fewer surgeries

If successful, the device will eliminate the need for open chest surgery in patients who aren’t candidates for transvenous placement. The ability to place these leads percutaneously should:

Reduce pain and infection risk.
Decrease procedure times.
Minimize surgery complications that arise from open surgery.
Improve better visualization for pericardial punctures.
Allow other novel therapies such as epicardial ablation or, in the future, even drug/gene delivery into the pericardial space.

Any implanted pacemaker or defibrillator must be replaced every 5-10 years. A young child in critical need of such devices could face surgeries 10 or more times to replace the device and/or leads.

Pre-clinical testing shows early data that this percutaneous approach is as safe and effective as an open surgical technique, although it remains in early-stage evaluation.

What’s next

The NIH SBIR funding will allow the research team to assess long-term safety and efficacy and commercialize the PeriPath tool. Next steps are to:

Refine the design of PeriPath for production manufacturing, integrate testing protocols into a Quality Management System and conduct a pilot verification build. Success is defined as manufacturing production devices that pass 510(k) verification and validation testing.
Demonstrate substantial equivalence to predicate trocars through performance and handling validation testing using PeriPath to implant an epicardial lead in a pediatric simulator. If successful, the team will demonstrate equivalence and obtain investigational device exception (IDE).
In the latter part of the plan, to perform a first in human feasibility clinical study using PeriPath to implant a commercial pacemaker lead with institutional review board (IRB) approval in infants at Children’s National.

Bottom line

Dr. Berul says, “This research could have a transformative impact on current clinical practice by converting an open surgical approach to a minimally invasive percutaneous procedure.”

He also notes that while the study design focuses on the unique needs of infants and children with congenital heart disease – who are the primary focus of the device – the results of the trial may benefit thousands of adult patients who need pacemakers or defibrillators but who are not candidates for the transvenous placement.

Children’s National provides clinical validation, IP for health challenge designed to advance pediatric innovation

June 24, 2021

girl with smart brain imagination doodle

Reinforcing its commitment to expanding innovation in pediatric care, Children’s National Hospital has joined a strategic partnership with the Center for Advancing Innovation (CAI) , along with collaborators Resonance Philanthropies and Digital Infuzion, to launch the 2021-2022 Innovate Children’s Health Challenge. This year’s event, Innovate Children’s Health II, focuses on technologies that address pandemic resiliency and prevention in the pediatric population and seeks to advance diagnostics, therapeutics and digital health tools that address pediatric mental health.

The initiative matches entrepreneurial talent with breakthrough inventions to launch startups and connect them with capital. For this challenge, more than 15 startups will compete for the opportunity to commercialize promising mental health solutions from a variety of research partners, including Children’s National. Nationally recognized for its expertise and commitment to innovation in pediatric care, Children’s National will contribute to the clinical validation of selected technologies.

“In addition to our role in providing clinical validation, this initiative provides the opportunity for intellectual property (IP) developed by leading clinicians at Children’s National Hospital, as well as other great pediatric institutions, to be considered for partnership with entrepreneurs who can help bring these technologies to market,” says Kolaleh Eskandanian, PhD, MBA, PMP, vice president and chief innovation officer at Children’s National Hospital. “Our mission is to improve children’s healthcare and Innovate Children’s Health II is a great way to harness this trifecta model — innovation, talent and capital — in order to develop breakthrough solutions that address the unique needs of pediatric patients.”

“In addition to our role in providing clinical validation, this initiative provides the opportunity for intellectual property (IP) developed by leading clinicians at Children’s National Hospital, as well as other great pediatric institutions, to be considered for partnership with entrepreneurs who can help bring these technologies to market,” says Kolaleh Eskandanian, PhD, MBA, PMP, vice president and chief innovation officer at Children’s National Hospital.

There are three ways to participate in Innovate Children’s Health II:

Entrepreneurial-minded people, alone or as members of multidisciplinary teams, may compete to commercialize vetted inventions;
Existing startups may enter the challenge with other public health-related inventions, including their own and/or others to which they have access;
Participants may submit ideas that they believe will improve emergency preparedness and pandemic response.

Inventors and technology licensing officers may submit inventions to be evaluated and made available for licensing to challenge winners. Innovate Children’s Health II will accept invention submissions until September 1, 2021. Anyone with an entrepreneurial spirit and interest in stopping current and future pandemics is invited to sign up to learn more about the challenge. Teams may also enroll in the challenge to choose a featured invention, bring in a third-party invention or get matched with an invention based on area of interest.

“The COVID-19 pandemic has made our children anxious, depressed and pessimistic about their futures. Through Innovate Children’s Health II, CAI and our strategic partner Children’s National will strive to give our children hope,” says Rosemarie Truman, founder and CEO of CAI. “We are grateful to Digital Infuzion and Resonance Philanthropies for their support, which makes this challenge possible.”

Eskandanian adds that supporting and expanding pediatric innovation is a key focus of the new Children’s National Research & Innovation Campus, the first-of-its-kind focused on pediatric health care innovation, with the first phase currently open on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on-site incubator Johnson and Johnson Innovation – JLABS, the campus provides a rich ecosystem of public and private partners which will help bolster pediatric innovation and commercialization.

Creating accessible platforms for innovation is essential to advancing children’s health

April 12, 2021

newborn baby

Children’s National Hospital continues in its efforts to educate and advocate about ways to address the unique challenges facing pediatric medical device innovation, such as small market size and a lack of industry investment. In a recent commentary for IEEE Pulse, the publication of the IEEE Engineering in Medicine and Biology Society, Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of the National Capital Consortium for Pediatric Device Innovation (NCC-PDI), discussed how the FDA and children’s hospitals are stepping in to bridge critical funding gaps and build an accessible infrastructure that safely accelerates the development and commercialization of pediatric medical devices.

“Our goal is to provide direct funding [with] expert advising and support services to innovators of pediatric medical devices,” says Eskandanian.

“Our goal is to provide direct funding [with] expert advising and support services to innovators of pediatric medical devices,” says Eskandanian. “The notion that innovation follows investment, that really gave us the idea of competitions where if we announced a challenge and we could put grant money behind it—and open it to the entire world — then we could attract small businesses and start-up companies that could come forward and start thinking about developing a medical device more specifically for the pediatric population.”

Now in its 8^th year, NCC-PDI’s “Make Your Medical Device Pitch for Kids!” competition focuses on identifying and supporting innovators that address specific unmet pediatric needs. This year’s competition focuses on innovations in pediatric devices that treat congenital heart disease (CHD), with an emphasis on electrophysiology (EP) devices such as pacemaker systems, ablation catheters, wearable monitoring devices and related technologies that address arrhythmias in children. While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period.

To learn more about the consortium’s efforts to advance pediatric innovation, visit the NCC-PDI website.

Medical device pitch competition focuses on pediatric electrophysiology devices for CHD

March 25, 2021

While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period.

Congenital heart disease (CHD) affects six out of 1,000 babies born in the U.S. each year and is often complicated by arrhythmias, a condition where the heart beats too rapidly, too slowly or irregularly due to a misfiring of the body’s electrical impulses. While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period. As a result, pediatric specialists are often using off-label or improvised devices to treat pediatric arrhythmias, including the smallest newborns.

Recognizing this unmet need, the National Capital Consortium for Pediatric Device Innovation (NCC-PDI), in collaboration with MedTech Innovator, is accepting applications through April 12, 2021, for its annual “Make Your Medical Device Pitch for Kids!” competition. This year’s competition focuses on innovations in pediatric devices that treat CHD, with an emphasis on electrophysiology devices such as pacemaker systems, ablation catheters, wearable monitoring devices and related technologies that address arrhythmias in children.

“NCC-PDI was created, with the support of the Food and Drug Administration (FDA), to seek out and address significant unmet needs in pediatric medical devices,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “We have learned from the experts that pediatric-specific technologies for treating arrhythmias would be a game changer in the care of their patients, so we are focusing our competition and grant awards on this opportunity.”

“We have learned from the experts that pediatric-specific technologies for treating arrhythmias would be a game changer in the care of their patients, so we are focusing our competition and grant awards on this opportunity,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI.

Using a virtual format, semi-finalists chosen from all submissions will make their first pitch on May 12, 2021. Up to 10 finalists selected from this event earn participation in a special pediatric-focused track of the MedTech Innovator accelerator program, the largest medtech accelerator in the world, beginning in June 2021. These innovators then participate in the pediatric competition finals in September 2021 where judges will award up to $150,000 in FDA-sponsored grants to the devices selected as most impactful and commercially viable.

How significant is the need for pediatric devices to address arrhythmias? In a recent survey of members conducted by the Pediatric and Congenital Electrophysiology Society (PACES), the vast majority (96%) said they believe there is a deficiency in devices available to serve the needs of pediatric patients. Conducted with the U.S.FDA, the survey also asked respondents to identify the biggest unmet need, which physicians identified as cardiovascular implantable electronic devices that are smaller, have better battery life and have pediatric-specific algorithms. Specifically, a leadless pacemaker designed for pediatric care was consistently on the most-wanted list.

NCC-PDI is one of five members in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children, which lags significantly behind the advancement of adult medical devices. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and the A. James Clark School of Engineering at the University of Maryland with support from partners MedTech Innovator, BioHealth Innovation and design firm Archimedic.

Eskandanian says that enhancing access to resources for pediatric innovators is also one of the aims of the Children’s National Research & Innovation Campus, a first-of-its-kind focused on pediatric health care innovation, with the first phase currently open on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on-site incubator Johnson and Johnson Innovation – JLABS, the campus provides a rich ecosystem of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

A new prototype for tiny pacemakers, faster surgery

November 13, 2018

Charles Berul, M.D., chief of cardiology at Children’s National, and Rohan Kumthekar, M.D., a cardiology fellow working in Dr. Berul’s bioengineering lab at the Sheikh Zayed Institute for Pediatric Surgical Innovation, explore ways to make surgical procedures for infants and children less invasive.

Rohan Kumthekar, M.D., a cardiology fellow working in Dr. Charles Berul’s bioengineering lab at the Sheikh Zayed Institute for Pediatric Surgical Innovation, part of Children’s National Health System, presented a prototype for a miniature pacemaker at the American Heart Association’s Scientific Sessions 2018 on Sunday, Nov. 11. The prototype, approximately 1 cc, the size of an almond, is designed to make pacemaker procedures for infants less invasive, less painful and more efficient, measured by shorter surgeries, faster recovery times and reduced medical costs.

Kumthekar, a Cardiovascular Disease in the Young Travel Award recipient, delivered his oral abstract, entitled “Minimally Invasive Percutaneous Epicardial Placement of a Custom Miniature Pacemaker with Leadlet under Direct Visualization,” as part of the Top Translational Science Abstracts in Pediatric Cardiology session.

“As cardiologists and pediatric surgeons, our goal is to put a child’s health and comfort first,” says Kumthekar. “Advancements in surgical fields are tending toward procedures that are less and less invasive. There are many laparoscopic surgeries in adults and children that used to be open surgeries, such as appendix and gall bladder removals. However, placing pacemaker leads on infants’ hearts has always been an open surgery. We are trying to bring those surgical advances into our field of pediatric cardiology to benefit our patients.”

Instead of using open-chest surgery, the current standard for implanting pacemakers in children, doctors could implant the tiny pacemakers by making a relatively tiny 1-cm incision just below the ribcage.

“The advantage is that the entire surgery is contained within a tiny 1-cm incision, which is what we find groundbreaking,” says Kumthekar.

With the help of a patented two-channel, self-anchoring access port previously developed by Berul’ s research group, the operator can insert a camera into the chest to directly visualize the entire procedure. They can then insert a sheath (narrow tube) through the second channel to access the pericardial sac, the plastic-like cover around the heart. The leadlet, the short extension of the miniature pacemaker, can be affixed onto the surface of the heart under direct visualization. The final step is to insert the pacemaker into the incision and close the skin, leaving a tiny scar instead of two large suture lines.

The median time from incision to implantation in this thoracoscopic surgery study was 21 minutes, and the entire procedure took less than an hour on average. In contrast, pediatric open-heart surgery could take up to several hours, depending on the child’s medical complexities.

“Placing a pacemaker in a small child is different than operating on an adult, due to their small chest cavity and narrow blood vessels,” says Kumthekar. “By eliminating the need to cut through the sternum or the ribs and fully open the chest to implant a pacemaker, the current model, we can cut down on surgical time and help alleviate pain.”

The miniature pacemakers and surgical approach may also work well for adult patients with limited vascular access, such as those born with congenital heart disease, or for patients who have had open-heart surgery or multiple previous cardiovascular procedures.

The miniature pacemakers passed a proof-of-concept simulation and the experimental model is now ready for a second phase of testing, which will analyze how the tailored devices hold up over time, prior to clinical testing and availability for infants.

“The concept of inserting a pacemaker with a 1-cm incision in less than an hour demonstrates the power of working with multidisciplinary research teams to quickly solve complex clinical challenges,” says Charles Berul, M.D., a guiding study author, electrophysiologist and the chief of cardiology at Children’s National.

Berul’s team from Children’s National collaborated with Medtronic PLC, developers of the first implantable pacemakers, to develop the prototype and provide resources and technical support to test the minimally-invasive surgery.

The National Institutes of Health provided a grant to Berul’s research team to develop the PeriPath, the all-in-one 1-cm access port, which cut down on the number of incisions by enabling the camera, needle, leadlet and pacemaker to be inserted into one port, through one tiny incision.

Other study authors listed on the abstract presented at Scientific Sessions 2018 include Justin Opfermann, M.S., Paige Mass, B.S., Jeffrey P. Moak, M.D., and Elizabeth Sherwin, M.D., from Children’s National, and Mark Marshall, M.S., and Teri Whitman, Ph.D., from Medtronic PLC.

Do plastic chemicals contribute to the sudden death of patients on dialysis?

September 5, 2018

Nikki Posnack, Ph.D., assistant professor with the Children’s National Heart Institute, continues to explore how repeat chemical exposure from medical devices influences cardiovascular function.

In a review published in HeartRhythm, Nikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, and Larisa Tereshchenko, M.D., Ph.D., FHRS, a researcher with the Knight Cardiovascular Institute at Oregon Health and Science University, establish a strong foundation for a running hypothesis: Replacing BPA- and DEHP- leaching plastics for alternative materials used to create medical devices may help patients on dialysis, and others with impaired immune function, live longer.

While Drs. Tereshchenko and Posnack note clinical studies and randomized controlled trials are needed to test this theory, they gather a compelling argument by examining the impact exposure to chemicals from plastics used in dialysis have on a patient’s short- and long-term health outcomes, including sudden cardiac death (SCD).

“As our society modifies our exposure to plastics to mitigate health risks, we should think about overexposure to plastics in a medical setting,” says Posnack. “The purpose of the review in HeartRhythm is to gather data about the impact chemical compounds, leached from plastic devices, have on cardiovascular outcomes for patients spending prolonged periods of time in the hospital.”

In this review, the authors explore chemical risk exposures in a medical setting, starting with factors that influence sudden cardiac death (SCD) among dialysis patients.

Why study dialysis patients?

SCD in dialysis patients accounts for one-third of deaths in this population. This prompts a need to develop prevention strategies, especially among patients with end-stage renal disease (ESRD).

The highest mortality rate observed among dialysis patients is during the first year of hemodialysis, a dialysis process that requires a machine to take the place of the kidneys and remove waste from the bloodstream and replenish it with minerals, such as potassium, sodium and calcium. During this year, mortality during hemodialysis is observed more frequently during the first three months of treatment, especially among older patients.

Possible reasons for an increased risk of an earlier death include chemical exposure, which is casually associated with altered cardiac function, as well as genetic risks for irregular heart rhythms and heart failure. In the HeartRhythm review, Drs. Tereshchenko and Posnack analyze factors that influence mortality:

Hemodialysis treatment, dialysis, is associated with plastic chemical exposure

Drs. Tereshchenko and Posnack note that dialysis tubing and catheters are commonly manufactured using polyvinyl chloride (PVC) polymers. The phthalate plastics used to soften PVC can easily leech if exposed to lipid-like substances, like blood. Research shows phthalate chemical concentrations increase during a four-hour dialysis.

Di(2-ethylhexyl) phthalate (DEHP) is a common plastic used to manufacture dialysis tubes, thanks to its structure and economy.

Bisphenol-A (BPA) is another common material used in medical device manufacturing. From the membranes of medical tools to resins, or external coatings and adhesives, BPA leaves behind a chemical residue on PVC medical devices.

In reviewing the research, the authors find dialysis patients are often exposed to high levels of DEHP and BPA. The amount of exposure to these chemicals varies in regards to room temperature, time of contact, other circuit coatings and the flow rate of dialysis. A faster flow rate correlates with reductions in chemical leaching and lower mortality rates.

Plastic chemical exposure is casually associated with altered cardiac function

Drs. Tereshchenko and Posnack note a causal relationship already exists between chemicals absorbed from plastics and cardiovascular outcomes.

Dr. Posnack’s previous research found BPA concentrations impaired electrical conduction in neonatal cardiomyocytes – young, developing heart cells – potentially altering the heart’s normal rhythm and function.

To the best of their knowledge, no clinical research has been conducted on DEHP exposure and SCD. However, proof-of-concept models find in vivo phthalate exposure alters autonomic regulation, which can slow down natural heart-rate rhythm and create a lag in recovery time to stressful stimuli. For humans, this type of stressful stimulation would be equivalent to recovering from a bike ride, car accident, or in this case, ongoing dialysis treatment with impaired immune function.

In other models, BPA exposure has been shown to cause bradycardia, or a delayed heart rate. In excised whole heart models, BPA has also been shown to alter cardiac electrical activity.

Abnormal electrophysiological substrate in end-stage renal disease

Since the heart and kidneys work in tandem to transport blood throughout the body, and manage vital functions, such as our heart rate, blood flow and breathing, the authors cite additional factors that lead to ongoing heart and kidney problems, with a look at end-stage renal disease (ESRD).

General heart-function kidney risks include abnormal electrophysiological (EP) substrate, the underlying electrical activity of the cardiac tissue, and genetic risk factors, including the TBX3 gene, a gene associated with a unique positioning of the heart and SCD.

“We don’t want to cite alarm about having a medical procedure or about relying on external help, such as dialysis, for proper kidney function,” says Posnack. “Especially since dialysis is a life-saving medical intervention for patients with inadequate kidney function.”

Pre-existing abnormal EP substrate interacts with plastic chemical exposure in incident dialysis, which increases risk of SCD in genetically predisposed ESRD patients

To summarize their findings, Drs. Tereshchenko and Posnack list a handful of support areas, starting with observations about reductions in cardiovascular mortality and SCD following kidney transplants. They note hemodialysis catheters are associated with larger DEHP exposure and a higher risk of SCD, compared to arteriovenous fistulas, highways surgically created to connect blood from the artery to the vein.

Drs. Posnack and Tereshchenko also note a correlative observation about higher SCD rates observed six hours after hemodialysis, when peak levels of DEHP and BPA are circulating in the bloodstream.

To compare and control for these factors among dialysis patients, the researchers cite different mortality patterns with hemodialysis and peritoneal dialysis. Patients on hemodialysis experience higher mortality during the first year of treatment, compared to peritoneal dialysis, who have higher mortality rates after the second year of treatment. Hemodialysis relies on a machine to take the place of kidney function, while peritoneal dialysis relies on a catheter, a small tube surgically inserted into the stomach.

“Our goal is to build on our previous research findings by analyzing variables that have yet to be studied before, and to update the field of medicine in the process,” says Dr. Posnack. “This includes investigating the cardiovascular risks of using BPA- and DEHP-materials to construct medical devices. Ultimately, we hope to determine whether plastic materials contribute to cardiovascular risks, and investigate whether patients might benefit from the use of alternative materials for medical devices.

Drs. Tereshchenko and Posnack note that despite the associations between chemical exposure from medical devices and increased cardiovascular risks, there are no restrictions in the United States on the use of phthalates and BPA chemicals used to manufacture medical devices.

Their future research will explore how replacing BPA- and DEHP-leaching plastics influence mortality and morbidity rates of ESRD patients on dialysis, as well as other patients exposed to repeat chemical exposure, such as patients having cardiac surgery.

“We want to make sure we identify and then work to minimize any potential risks of plastic exposure in a medical setting,” adds Dr. Posnack. “Our goal is to put the health and safety of patients first.”

Dr. Posnack’s research is funded by two grants (R01HL139472, R00ES023477) from the National Institutes of Health.

NIH funding to improve devices and safeguard cardiovascular health

February 9, 2018

Nearly 15 million blood transfusions are performed each year in the U.S., and pediatric patients alone receive roughly 425,000 transfused units. Endocrine-disrupting chemicals, such as bisphenol A and di-2-ethylhexyl-phthalate (DEHP), can leach from some plastic devices used in such transfusions. However, it remains unclear how many complications following a transfusion can be attributed to the interplay between local and systemic reactions to these chemical contaminants.

Top: Live, excised heart that is being perfused with a crystalloid buffer via the aorta. The heart is stained with a voltage-sensitive fluorescent dye, which is excited by an LED light source. Bottom, right: Cardiac action potentials are optically mapped across the epicardial surface in real-time by monitoring changes in the fluorescence signal that are proportional to changes in transmembrane voltage. Bottom, left: An activation map (middle) depicts the speed of electrical conduction across the heart surface. Credit: Rafael Jaimes, Ph.D.; Luther Swift, Ph.D.; Manelle Ramadan, B.S.; Bryan Siegel, M.D.; James Hiebert, B.S., all of Children’s National Health System; and Daniel McInerney, student at The George Washington University.

The National Heart, Lung and Blood Institute within the National Institutes of Health has awarded a $3.4 million, five-year grant to Nikki Gillum Posnack, Ph.D., assistant professor at the Children’s National Heart Institute within the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National Health System, to answer that question and to provide insights that could accelerate development of safer biomaterials.

According to the Food and Drug Administration, patients who are undergoing IV therapy, blood transfusion, cardiopulmonary bypass or extracorporeal membrane oxygenation or who receive nutrition through feeding support tubes have the potential to be exposed to DEHP.

Posnack led a recent study that found that an experimental model exposed to DEHP experienced altered autonomic regulation, heart rate variability and cardiovascular reactivity and reported the findings Nov. 6, 2017, in the American Journal of Physiology. The pre-clinical model study is the first to show such an association between phthalate chemicals used in everyday medical devices like IV tubing and cardiovascular health.

In the follow-on research, Posnack and colleagues will:

Use in vivo and whole heart models to define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function in experimental models
Determine whether biocompatibility and incidental chemical exposure are linked to cardiovascular and autonomic abnormalities experienced by pediatric patients post transfusion
Compare and contrast alternative biomaterials, chemicals and manufacturing techniques to identify safer transfusion device options.

“Ultimately, we hope to strengthen the evidence base used to inform decisions by the scientific, medical and regulatory communities about whether chemical additives that have endocrine-disrupting properties should be used to manufacture medical devices,” Posnack says. “Our findings also will highlight incentives that could accelerate development of alternative biomaterials, additives and fabrication techniques to improve safety for patients undergoing transfusion.”

Experimental model study links phthalates and cardiovascular health

February 7, 2018

“Because phthalate chemicals are known to migrate out of plastic products, our study highlights the importance of adopting safer materials, chemical additives and/or surface coatings for use in medical devices to reduce the risk of inadvertent exposure,” explains study senior author Nikki Gillum Posnack, Ph.D.

An experimental model exposed to di-2-ethylhexyl-phthalate (DEHP), a chemical that can leach from plastic-based medical devices, experienced altered autonomic regulation, heart rate variability and cardiovascular reactivity, according to a study published online Nov. 6, 2017 by the American Journal of Physiology. The pre-clinical model study is the first to show such an association between phthalate chemicals used in everyday medical devices like IV tubing and cardiovascular health.

“Plastics have revolutionized medical devices, transformed how we treat blood-based diseases and helped to make innovative cardiology procedures possible,” says Nikki Gillum Posnack, Ph.D., study senior author and assistant professor at the Children’s National Heart Institute within the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National Health System. “Because phthalate chemicals are known to migrate out of plastic products, our study highlights the importance of adopting safer materials, chemical additives and/or surface coatings for use in medical devices to reduce the risk of inadvertent exposure.”

According to the Food and Drug Administration, patients who are undergoing IV therapy, blood transfusion, cardiopulmonary bypass or extracorporeal membrane oxygenation or who receive nutrition through feeding support tubes have the potential to be exposed to DEHP.

Patients undergoing extensive interventions to save their lives may be exposed to multiple plastic-based devices that supply oxygen and nutrition or that pump newly oxygenated blood to oxygen-starved organs.

“These interventions keep very fragile kids alive. What’s most important is getting patients the care they need when they need it,” Posnack says. “In the biomaterials field, our ultimate goal is to reduce inadvertent risks to patients that can result from contact with plastic products by identifying replacement materials or safer coatings to lower overall risk.”

In order to assess the safety of phthalate chemicals used in such medical devices, the Children’s-led research team implanted adult experimental models with radiofrequency transmitters that monitored their heart rate variability, blood pressure and autonomic regulation. Then, they exposed the experimental models to DEHP, a softener used in making the plastic polymer, polyvinyl chloride, flexible.

DEHP-treated pre-clinical models had decreased heart rate variability with lower-than-normal variation in the intervals between heart beats. The experimental models also showed an exaggerated mean arterial pressure response to ganglionic blockade. And in response to a stressor, the experimental models in the treatment group displayed enhanced cardiovascular reactivity as well as prolonged blood pressure recovery, according to the study team.

“The autonomic nervous system is a part of the nervous system that automatically regulates such essential functions as blood pressure and breathing rate without any conscious effort by the individual,” Posnack adds. “Because alterations in the autonomic balance provide an early warning sign of trouble – before symptoms of hypertension or atherosclerosis manifest – our findings underscore the importance of additional studies to explore the potential impact of phthalate chemicals on organ function.”

Billie Lou Short, M.D., chief of Children’s Division of Neonatology, called the paper an “important study” that builds on a foundation laid in the late 199os by Children’s researchers who were the first to show that plasticizers migrated from tubing in the extracorporeal membrane oxygenation (ECMO) circuit. Children’s researchers also led a study published in 2004 that evaluated the effect of plasticizers on the human reproductive system. A small number of adolescents who had undergone ECMO as newborns did not experience the complications that had been seen in in experimental models, Dr. Short says.

Posnack’s study co-authors include Rafael Jaimes III, Ph.D., SZI staff scientist; Meredith Sherman, SZI research technician; and Adam Swiercz, Narine Muselimyan and Paul J. Marvar, all of The George Washington University.

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