By Sofia Noejovich
Dr. Witzenburg designs models of the heart that predict how the heart will grow and change in response to cardiac heart diseases such as hypoplastic left heart syndrome (HLHS) to improve medical decision-making for clinicians.
When it comes to cardiac surgery, clinicians are under pressure to make timely and logical clinical decisions. Without any formal tools, clinicians rely on their experience and may struggle to decide not just what procedures to perform but also when to perform them. In the progression of medicine, an increasingly frequent topic of conversation is developing a more algorithmic approach to medical decision-making.
At UW-Madison, Dr. Colleen Witzenburg is researching ways to model structural changes in the heart to predict when and where surgery should be conducted in patients. Her background in mechanical engineering allows her to approach this problem by modeling the structural changes in cardiac biomaterials. “Biological material is complex in its response,” says Witzenburg, “In engineering classes, we are taught to use Young’s Modulus to predict stress and strain because manmade material is linear and predictable. But soft tissue does not have linear behavior; it is exponential or polynomial-like, it is anisotropic, and, in the case of the heart, contractile.”
Witzenburg focuses her research on modeling the hearts of babies born with hypoplastic left heart syndrome (HLHS). This congenital disability causes babies to be born with a weak or absent left ventricle, which is responsible for pumping oxygen-rich blood to the body. When the left ventricle is nonfunctional, the right ventricle will not only perform its original task of pumping blood to the lungs, but it will also assume the role of the left ventricle and deliver blood to the entire body. As the child develops, the demand for oxygen-rich blood increases and the right ventricle becomes overworked. Consequently, the child will be at significant risk for heart failure and will have an average of three open heart surgeries before the age of four. Therefore, understanding the effect stress has on the heart both acutely and over time is critical for the survival of the child.
Comprehending the structural response of the heart to HLHS can be understood from a mechanical perspective. Witzenburg explains that biologic tissues have unique material behaviors, the most important of which is their ability to adapt to changing conditions. First, an insult or a stressor causes physical damage to the heart or changes the loading on the heart’s ventricles. The heart must continue to meet the oxygen flow demands of the body, so there is increased stress and strain on the heart muscle. These increases result in the growth and remodeling of the ventricles, creating changes in thickness and dilation over time. However, as the geometry of the heart changes, the stress and strain change as well.
“Children born with HLHS often undergo multiple surgeries as they grow, but amazingly no methods currently exist to predict how a surgery will impact the shape and size of their heart.”
Different scenarios can occur when the heart grows and remodels in response to overload. In one scenario the heart will grow, resolve the stimulus, and return to homeostasis. In the second scenario, however, the heart growth may exacerbate the stimulus, inciting additional growth and creating what Witzenburg describes as a “runaway situation.” Understanding when and why each scenario occurs could be vital not just to clinical decision-making but also to the design of novel treatments.
While studying the structural changes occurring in the heart are important, understanding the time frame of these changes and failures is the deciding factor in the survival of patients with HLHS. An added complication of this disease is that infants grow rapidly, tripling their weight in their first year. When it comes to surgery, it is preferable that clinicians conduct operations on larger and more developed hearts. However, while it is better to wait to perform surgery until they are more fully developed, changes in the heart can cause permanent damage if clinicians wait too long. “When is the sweet spot in these two time frames?” asks Witzenburg, “Our goal is to forecast various outcomes for a patient — giving clinicians a tool that finally addresses what they care about — improvement in function for the long-term.”
To better understand the time frame of these structural changes, Witzenburg hopes to project with her models when these two situations are likely to occur. In 2018 at the University of Virginia, she published a paper on a model that could predict the timing of ventricular dilation and thickening in dogs experiencing heart failure. She is especially thankful to her mentor at the University of Virginia, Jeffrey Holmes, and is happy to be adapting this model to congenital heart disease with a team of talented students at UW-Madison. They are currently focused on patients with HLHS and aim to predict the course of dilation and thickening in their hearts. Her team is using retrospective data to adapt her computational approach. One of the most significant challenges Witzenburg faces is to validate the model. She claims that a considerable part of this research is going back and forth with her model used for dogs and ensuring the parameters are adjusted to human physiology by checking against the data both for adults and infants.
Tools for better decision-making enable clinicians to be more systematic and analytical with their choices. They also make it possible for clinicians to consider larger data sets and incorporate a patient’s unique background, anatomy, and physiology. Witzenburg reiterates, however, that these tools could never replace clinicians. “Congenital heart defects involve complicated changes in the anatomy of the heart and blood vessels that are unique to each child, making them among the most challenging problems in all of medicine. Our goal is to create tools that assist multidisciplinary teams — cardiologists, surgeons, imaging specialists — in deciding on the best course for each patient.” The research Witzenburg and her team are undertaking will help clinicians all over the world to better succeed in treating patients with cardiac abnormalities.