BackgroundCurrent risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network (BN) based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0.MethodsWe derived a Tree Augmented Naïve Bayes model (titled PHORA) to predict one-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in COMPERA and PHSANZ registry). Patients were classified as low, intermediate and high-risk (<5%, 5-20% and>10% 12-month mortality, respectively) based on the 2015 ESC/ERS guidelines.ResultsPHORA had an AUC of 0.80 for predicting one-year survival, which was an improvement over REVEAL 2.0 (AUC of 0.76). When validated in COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80 respectively. One-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (P<.001), with excellent separation between low-, intermediate-, and high-risk groups in all three registries.ConclusionOur BN derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of BN based model's ability to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.

Purpose of Review Pulmonary arterial hypertension (PAH) is a chronic, progressive, and incurable disease with significant morbidity and mortality. Despite increasingly available treatment options, PAH patients continue to experience disease progression and increased rates of hospitalizations due to right heart failure. Physician’s ability to comprehensively assess PAH patients, determine prognosis, and monitor disease progression and response to treatment remains critical in optimizing outcomes. Recent Findings Risk assessment in PAH should include a range of clinical, hemodynamic, and exercise parameters, performed in a serial fashion over the course of treatment. Approaches to risk assessment in PAH patients include the use of risk variables, scores, and equations that stratify the impact of both modifiable (e.g., 6-min walk distance, functional class, brain natriuretic peptide), and non-modifiable (e.g., age, gender, PAH etiology) risk factors. Such tools allow physicians to better determine prognosis, allocate treatment resources, and enhance the consistency of treatment approaches across providers. Summary Comprehensive and accurate risk prediction is essential to make individualized treatment decisions and optimizing outcomes in PAH.

Pulmonary arterial hypertension (PAH) is a chronic and rapidly progressive disease that is characterized by extensive narrowing of the pulmonary vasculature, leading to increases in pulmonary vascular resistance, subsequent right ventricular dysfunction, and eventual death. There are currently multiple approved drugs—developed as single or combination therapies in the last few years—that have improved outcome and functionality in PAH. However, despite improvement in short-term survival with these new effective therapies, PAH remains an incurable disease with a median survival of 7 years (Figure 1).1 This chronic disease state may be characterized by morbid events such as hospitalizations that herald rapid disease progression and account for a significant disease burden (Figure 2).23 Physician ability to predict PAH disease progression is critical for determining optimal care of patients. Accurate risk assessment allows clinicians to determine the patient's prognosis, identify treatment goals, and monitor disease progression and the patient's response to treatment. Risk assessment for PAH patients should include a range of clinical, hemodynamic, and exercise parameters, performed in a serial fashion over the treatment course. Patient risk stratification can also help physicians better allocate treatment resources in settings where they are scarce. If widely adopted, risk prediction can enhance the consistency of treatment approaches across PAH practitioners and improve the timeliness of referral for lung transplantation. Hence, along with advancing PAH treatment options, comprehensive risk prediction is essential to make individualized treatment decisions in the current treatment era. Several tools are currently available for assessing risk in PAH (Figure 3). These include the 2015 European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines' risk variables,4 the French registry equation,5 the National Institutes of Health risk equation,6 or a risk score such as the one derived from the Registry to Evaluate Early And Long-term PAH Disease Management.1 These registries and evaluations of clinical trial sets have provided important insights into the importance of both modifiable (eg, 6-minute walk distance, functional class, brain natriuretic peptide, and nonmodifiable (eg, age, gender, PAH etiology) risk factors that predict survival. The following review explores commonly cited risk factors, both modifiable and nonmodifiable, and their implications for patient outcomes.

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Cox’s proportional hazards (CPH) model is quite likely the most popular modeling technique in survival analysis. While the CPH model is able to represent a relationship between a collection of risks and their common effect, Bayesian networks have become an attractive alternative with an increased modeling power and far broader applications. Our paper focuses on a Bayesian network interpretation of the CPH model (BN-Cox). We provide a method of encoding knowledge from existing CPH models in the process of knowledge engineering for Bayesian networks. This is important because in practice we often have CPH models available in the literature and no access to the original data from which they have been derived. We compare the accuracy of the resulting BN-Cox model to the original CPH model, Kaplan-Meier estimate, and Bayesian networks learned from data, including Naive Bayes, Tree Augmented Naive Bayes, Noisy-Max, and parameter learning by means of the EM algorithm. BN-Cox model came out as the most accurate of all BN approaches and very close to the original CPH model. We study two approaches for simplifying the BN-Cox model for the sake of representational and computational efficiency: (1) parent divorcing and (2) removing less important risk factors. We show that removing less important risk factors leads to smaller loss of accuracy.

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