Predicting Physiological Response in Heart Failure Management: A Graph Representation Learning Approach using Electronic Health Records

Heart failure management is challenging due to the complex and heterogenous nature of its pathophysiology which makes the conventional treatments based on the “one size fits all” ideology not suitable. Coupling the longitudinal medical data with novel deep learning and network-based analytics will enable identifying the distinct patient phenotypic characteristics to help individualize the treatment regimen through the accurate prediction of the physiological response. In this study, we develop a graph representation learning framework that integrates the heterogeneous clinical events in the electronic health records (EHR) as graph format data, in which the patient-specific patterns and features are naturally infused for personalized predictions of lab test response. The framework includes a novel Graph Transformer Network that is equipped with a self-attention mechanism to model the underlying spatial interdependencies among the clinical events characterizing the cardiac physiological interactions in the heart failure treatment and a graph neural network (GNN) layer to incorporate the explicit temporality of each clinical event, that would help summarize the therapeutic effects induced on the physiological variables, and subsequently on the patient’s health status as the heart failure condition progresses over time. We introduce a global attention mask that is computed based on event co-occurrences and is aggregated across all patient records to enhance the guidance of neighbor selection in graph representation learning. We test the feasibility of our model through detailed quantitative and qualitative evaluations on observational EHR data. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Institute of Health (NIH) NIGMS (R00GM135488) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Mayo Clinic gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data used in the present study are PHI so cannot be made publicly available.