CARNA: Characterizing Advanced heart failure Risk and hemodyNAmic phenotypes using learned multi-valued decision diagrams

Abstract: Early identification of high risk heart failure (HF) patients is key to timely allocation of life-saving therapies. Hemodynamic assessments can facilitate risk stratification and enhance understanding of HF trajectories. However, risk assessment for HF is a complex, multi-faceted decision-making process that can be challenging. Previous risk models for HF do not integrate invasive hemodynamics or support missing data, and use statistical methods prone to bias or machine learning methods that are not interpretable. To address these limitations, this paper presents CARNA, a hemodynamic risk stratification and phenotyping framework for advanced HF that takes advantage of the explainability and expressivity of machine learned Multi-Valued Decision Diagrams (MVDDs). This interpretable framework learns risk scores that predict the probability of patient outcomes, and outputs descriptive patient phenotypes (sets of features and thresholds) that characterize each predicted risk score. CARNA incorporates invasive hemodynamics and can make predictions on missing data. The CARNA models were trained and validated using a total of five advanced HF patient cohorts collected from previous trials, and compared with six established HF risk scores and three traditional ML risk models. CARNA provides robust risk stratification, outperforming all previous benchmarks. Although focused on advanced HF, the CARNA framework is general purpose and can be used to learn risk stratifications for other diseases and medical applications.