Abstract
Background Current 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.
Methods We 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.
Results PHORA 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.
Conclusion Our 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Kanwar reports grants from NIH/NHBLI, during the conduct of the study.
Conflict of interest: Dr. Gomberg-Maitland reports consultancy/Steering Committee, DSMB from Acceleron, Actelion, Complexa, Gossamer Bio, Reata, and Neuroderm. George Washington has received grants for research from Altavant and United Therapeutics. She is a member of the Scientific Advisory Board for United Therapeutics, outside the submitted work.
Conflict of interest: Dr. Hoeper reports personal fees from Actelion, personal fees from Bayer, personal fees from MSD, personal fees from Pfizer, outside the submitted work.
Conflict of interest: Dr. Pausch has nothing to disclose.
David Pittow
Conflict of interest: Dr. Strange reports grants from Actelion Pharmaceuticals, grants from GlasoSmithKline , grants from Bayer Pharmaceuticals, during the conduct of the study.
Conflict of interest: Dr. Anderson reports grants from GlaxoSmithKline, non-financial support from Actelion, non-financial support from Bayer, personal fees from AstraZeneca, outside the submitted work.
Conflict of interest: Carol Zhao reports personal fees from Actelion Pharmaceuticals US, Inc., A Janssen Pharmaceutical Company of Johnson & Johnson, during the conduct of the study; personal fees from Actelion Pharmaceuticals US, Inc., A Janssen Pharmaceutical Company of Johnson & Johnson, outside the submitted work.
Conflict of interest: Dr. Scott has nothing to disclose.
Conflict of interest: Dr. Druzdzel is a partner at BayesFusion, LLC.
Conflict of interest: Dr. Kraisangka has nothing to disclose.
Lisa Lohmueller
Conflict of interest: Dr. Antaki reports grants from NIH/NHLBI, during the conduct of the study.
Conflict of interest: Dr. Benza reports grants from NIH/NHLBI, grants from Actelion, grants from United Therapeutics, grants from Bayer, during the conduct of the study.
Conflict of interest: Dr. Lohmueller has nothing to disclose.
Conflict of interest: Dr. Pittrow reports personal fees from Actelion, personal fees from Bayer, personal fees from Amgen, personal fees from Boehringer Ingelheim, personal fees from Sanofi, personal fees from MSD, personal fees from Biogen, outside the submitted work.
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- Received January 9, 2020.
- Accepted April 21, 2020.
- Copyright ©ERS 2020
