3D Printers Provide a Window into the Heart
Performing a transcatheter aortic valve replacement (TAVR) on a patient with congenital heart disease can force an interventional cardiologist to navigate uncharted anatomic territory. When the patient’s anatomy is complex, procedures such as placing a new heart valve can take longer and are associated with a higher risk for various complications.
However, some cardiologists are turning to a new tool to help them prepare for such complex procedures—three-dimensional (3D) printers, which can use computed tomography scans to generate a model of the patient’s precise anatomy to prepare for the surgery.
“The 3D printing allows us to have a 3D model that can be held in hand and shown to the interventional cardiologists and surgeons doing the procedure,” said Ron Blankstein, MD, codirector of the Cardiovascular Imaging Training program at Brigham and Women’s Hospital in Boston and Associate Professor of Medicine and Radiology at Harvard Medical School. “It is particularly useful in cases where the anatomy is not straightforward.”
These 3D printers are becoming a fixture at many academic centers, where the printers and expert staff are often hired to help convert imaging into 3D models that can be used by surgeons and interventional cardiologists preparing for many types of surgeries and procedures. In addition to clinical applications, the technology is also being applied in basic research where scientists use it to print living cells into complex 3D structures called organoids, which re-create many features of the heart. These heart organoids are proving to be a valuable research tool and could be a future source for engineered tissue transplants.
Finding a Better Fit
One of the big challenges for interventional cardiologists preparing for TAVR is making sure they choose a prosthetic value that fits well, explained Blankstein. An ill-fitting valve is more likely to be associated with paravalvular leaks, a known poor prognostic factor, and other potential complications. With transcatheter mitral valves on the horizon, 3D models may take on added importance given the complexities and variations in mitral valve anatomy. For instance, models can be used to predict the likelihood of obstruction of the left ventricular outflow tract from a large valve in the mitral position. At present, physicians typically rely on 2D models generated from imaging studies to select the best valve.
Blankstein and his colleagues, however, recently published a proof-of-concept study in the Journal of Cardiovascular Computed Tomography assessing how well a 3D model would predict which patient-valve combinations are likely to lead to paravalvular regurgitation. They used cardiac computed tomography imaging data from 16 patients who had undergone TAVR, 9 whose valves came loose after the procedure and 7 whose valve stayed in place. The 3D models would have predicted 6 of the 9 regurgitant valves, and it would have accurately predicted 5 of the 7 successful procedures.
The results suggest promise in this potential use of 3D printers in TAVR, but more work is needed. To date, no randomized studies have assessed whether 3D printed models can improve patient outcomes; such a study might be difficult to conduct because regurgitations are becoming increasingly rare, Blankstein noted.
“The entire field is exciting and new, but we still have to establish where it has a role and where it can actually improve patient care,” Blankstein noted.
At present, producing 3D models is time consuming and labor intensive, Blankstein noted. For example, the total production time for each 3D model in the study was ≥5 hours. Some academic centers have the facilities and expertise on site to create them, but others must send the imaging data to outside companies to produce them.
The models are not necessary for less complicated cases, he said. However, he and his colleagues are using 3D printed models in select cases where they think it could add value. In addition to using 3D models for planning valvular heart procedures, Blankstein and colleagues are also using this technique for complex congenital heart disease cases.
Future improvements in the 3D models may increase their value. For example, models that are printed with a more flexible material that mimics the elasticity of the heart may be more useful. The more rigid models created now can be misleading, noted Blankstein. He explained that the heart is larger during diastole than systole, so a rigid model based on an image taken during systole may not always provide all the information needed.
“This is an evolving tool that allows us to better understand individual patient anatomy before the TAVR procedure and ultimately has the potential to improve and further individualize patient care,” he said.
Researchers in many fields have embraced the use of 3D printers to build organoids they can use to study physiology and disease in the laboratory. Among them is Ali Khademhosseini, PhD, an engineer and professor at Harvard Medical School, who recently developed a heart organoid that may aid with drug screening.
To do this, he and his colleagues had to create an environment in the laboratory that makes cardiac cells “feel comfortable and start acting like heart cells.” He explained that coaxing stems cells to mature into heart cells in the laboratory can be a challenge. So, he and his colleagues tried to re-create the environment in the heart by creating a bioreactor that provides electric stimulation and surrounds the cells with a medium that matches the mechanical properties of heart endothelium.
“We used a lot of tissue engineering tricks,” he said.
To produce cardiac tissue, stems cells are mixed with a gel and then forced through the nozzle of a 3D bioprinter, which can closely re-create the structure of heart tissue and even print in vasculature. Together the 3D-printed tissue and the bioreactor create what Khademhosseini describes as a heart-on-a-chip.
The immediate application for this technology is screening drugs for cardiac toxicity. For example, Khademhosseini and his team exposed their heart-on-a-chip to the cancer drug doxorubicin and found that both the heart muscle and endothelial cells responded in a dose-dependent fashion, according to a 2016 study they published in the journal Biomaterials.
The technology could be used to screen the cardiac effects of hundreds or even thousands of drugs simultaneously, hopefully speeding up drug screening. One day it may allow scientists to skip using rodent models and instead test drug toxicity in human organoids in the laboratory, Khademhosseini said. It may also advance personalized medicine by allowing scientists to grow organoids from cells collected from individuals with genetic disorders or disease, allowing scientist to see how drugs would effect that individual.
Already some scientists are exploring transplants of laboratory grown cells as treatment, but that is just the start.
“The idea is that if we can get good at this, then one day we make larger pieces of heart tissue or the full heart for transplant applications,” Khademhosseini said.
Circulation is available at http://circ.ahajournals.org.
- © 2017 American Heart Association, Inc.