Seeking to Determine Optimal Timing for Important Interventions in Adult Patients With Repaired Congenital Heart Diseases
In This Article
- Due to shortcomings in clinical guidelines, determining optimal timing of important interventions in adult patients with repaired congenital heart diseases remains an inexact and incompletely understood process
- A recently published paper outlines a theoretical framework for solving this complex challenge
- The proposed novel approach, based on a mathematical technique known as optimal stopping theory, derives patient-specific thresholds to inform decision-making about timing for potential interventions
Due to shortcomings in clinical guidelines, determining optimal timing of important interventions in adult patients with repaired congenital heart diseases remains an inexact and incompletely understood process.
Subscribe to the latest updates from Cardiovascular Advances in Motion
Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) is a commonly required intervention. For clinicians, it can be difficult to determine which patients will benefit from earlier intervention with PVR, even if they do not have symptoms, and which patients may not.
A paper recently published in the International Journal of Cardiology Congenital Heart Disease by Massachusetts General Hospital adult congenital heart disease (ACHD) specialist Sihong Huang, MD, and colleagues outlines a novel theoretical framework for solving this complex challenge using determination of timing for PVR in patients with rTOF as an example.
The proposed approach is based on a mathematical technique known as optimal stopping theory. The methodology derives patient-specific thresholds to inform decision-making about PVR timing (but can be applied to many other situations as well). If the patient's clinical status falls between the two calculated thresholds, PVR is considered appropriate. If the score falls outside the thresholds, the patient is deemed either too unwell or too well to undergo the procedure.
"The guidelines that we have now are less ideal and not patient-specific," says Dr. Huang, the paper's senior author. "Our hope is to provide clinicians with objective data that account for the patient's individual risk factors and disease progression, thus complementing existing guidelines on timing of PVR in this patient population."
Drawing on the Expertise of an Economist
For an ACHD conference that Dr. Huang organized in 2022, she invited economist Laura Delaney, PhD, of King's College Business School in London. Dr. Delaney, who has a history of hypoplastic left heart syndrome, had undergone the Fontan procedure and then, after developing Fontan failure, a heart transplant. She subsequently had two successful pregnancies. At the event, she gave a talk on "Determining the Optimal Transplant Listing Window for Patients with Fontan Physiology."
During a subsequent conversation over lunch, Dr. Huang asked Dr. Delaney about her research interests.
"She said, 'I do a lot of modeling and predicting in economics,'" Dr. Huang recalls. "I mentioned that I would love to be able to predict when we should do heart transplants in Fontan patients. As it turned out, she had previously published a paper about developing potential models for this very purpose."
After recruiting an ACHD specialist and a statistician for the effort, Drs. Huang and Delaney set out to develop a model to help optimize determination of timing of interventions such as PVR in rTOF patients. Dr. Huang's dream is to develop a model for Fontan transplant timing prediction. However, the team decided to first prove the model's effectiveness with rTOF patients, a much larger population than that of Fontan patients.
The stakes of this work are high, as performing PVR or transplantation at the optimal time is associated with a reduction in morbidity and mortality along with an improvement in functional capacity, quality of life, and life expectancy.
A Timing Model Based on Optimal Stopping Theory
Dr. Huang and her colleagues derived a timing model for PVR in patients with rTOF based on optimal stopping theory. A strategy used most commonly in finance and economics, optimal stopping theory aims to pinpoint when to take an irreversible action in the face of uncertainty to maximize the likelihood of the best outcome.
To apply their model, the research team first identified four patient-specific inputs:
- Clinical score based on indicators from cardiac MRI, the cardiopulmonary exercise test, and many other clinical parameters
- Outcome, with definitions of good and poor outcomes based on related studies in the literature
- Rate of clinical decline, in which the patient is scored based on their acquired risk factors at the time of intervention/treatment and six to 12 months prior
- Rate of time preference, which references how much value is assigned to the patient's current clinical state over their future well-being
By plugging these four inputs into a formula, a clinical score is calculated for the patient. Upper (kH) and lower (kL) thresholds are also established. If the score is above the kH value, the patient is considered too well for PVR, and the clinician should adopt a "watchful waiting" approach. If it is below the kL value, the patient is considered too sick for PVR in their current clinical state.
Dr. Huang and her colleagues plan next to validate the model with clinical data drawn from a large cohort of patients who have undergone PVR.
"We want to retrospectively apply this model to those patients to see how it performs," she says. "Based on the actual outcome, is our model correct when it predicts a patient should or shouldn't have PVR?"
Achieving 80% correct recommendations would be the ideal, according to Dr. Huang, who adds that the model should be given further consideration for use in the clinical practice setting if it performs better than the clinicians.
"This is because we know all patients in the cohort ultimately underwent PVR," she explains. "Therefore, if the proposed model provides a correct recommendation for a higher percentage of patients than the current guidelines—meaning it identifies more patients who go on to have good outcomes and correctly recommends against PVR for at least one patient who experienced a poor outcome—then the model can be considered to outperform the current guideline."
The team's ultimate goal is to develop a model that can be modified to fit different disease processes for different decision-making in adults with congenital heart diseases. This would include determining the optimal timing for transplantation in patients with failing Fontan so that they can have the ideal outcome that Dr. Delaney has.
"This work has tremendous implications for the later health and long-term outlook for our young patients with congenital heart disease," says ACHD cardiologist Doreen DeFaria Yeh, MD. "If we can more precisely predict who will do very well with PVR, and who might not do well with PVR, we can better individualize our recommendations for patients and observe better long-term outcomes in our older ACHD patients."