A Network-Based “Phenomics” Approach for Discovering Patient Subtypes From High-Throughput Cardiac Imaging Data

Objectives: The authors present a method that focuses on cohort matching algorithms for performing patient-to-patient comparisons along multiple echocardiographic parameters for predicting meaningful patient subgroups. Background: Recent efforts in collecting multiomics data open numerous opportunities for comprehensive integration of highly heterogenous data to classify a patient's cardiovascular state, eventually leading to tailored therapies. Methods: A total of 42 echocardiography features, including 2-dimensional and Doppler measurements, left ventricular (LV) and atrial speckle-tracking, and vector flow mapping data, were obtained in 297 patients. A similarity network was developed to delineate distinct patient phenotypes, and then neural network models were trained for discriminating the phenotypic presentations. Results: The patient similarity model identified 4 clusters (I to IV), with patients in each cluster showed distinctive clinical presentations based on American College of Cardiology/American Heart Association heart failure stage and the occurrence of short-term major adverse cardiac and cerebrovascular events. Compared with other clusters, cluster IV had a higher prevalence of stage C or D heart failure (78%; p < 0.001), New York Heart Association functional classes III or IV (61%; p < 0.001), and a higher incidence of major adverse cardiac and cerebrovascular events (p < 0.001). The neural network model showed robust prediction of patient clusters, with area under the receiver-operating characteristic curve ranging from 0.82 to 0.99 for the independent hold-out validation set. Conclusions: Automated computational methods for phenotyping can be an effective strategy to fuse multidimensional parameters of LV structure and function. It can identify distinct cardiac phenogroups in terms of clinical characteristics, cardiac structure and function, hemodynamics, and outcomes.