Identifying Patients at Risk of Major Adverse Cardiovascular Events Using Symbolic Mismatch

Cardiovascular disease is the leading cause of death globally, resulting in 17 million deaths each year. Despite the availability of various treatment options, existing techniques based upon conventional medical knowledge often fail to identify patients who might have benefited from more aggressive therapy. In this paper, we describe and evaluate a novel unsupervised machine learning approach for cardiac risk stratification. The key idea of our approach is to avoid specialized medical knowledge, and assess patient risk using symbolic mismatch, a new metric to assess similarity in long-term time-series activity. We hypothesize that high risk patients can be identified using symbolic mismatch, as individuals in a population with unusual long-term physiological activity. We describe related approaches that build on these ideas to provide improved medical decision making for patients who have recently suffered coronary attacks. We first describe how to compute the symbolic mismatch between pairs of long term electrocardiographic (ECG) signals. This algorithm maps the original signals into a symbolic domain, and provides a quantitative assessment of the difference between these symbolic representations of the original signals. We then show how this measure can be used with each of a one-class SVM, a nearest neighbor classifier, and hierarchical clustering to improve risk stratification. We evaluated our methods on a population of 686 cardiac patients with available long-term electrocardiographic data. In a univariate analysis, all of the methods provided a statistically significant association with the occurrence of a major adverse cardiac event in the next 90 days. In a multivariate analysis that incorporated the most widely used clinical risk variables, the nearest neighbor and hierarchical clustering approaches were able to statistically significantly distinguish patients with a roughly two-fold risk of suffering a major adverse cardiac event in the next 90 days.