Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Author is also affiliated with the MIT Dept. of Electrical Engineering and Computer Science. Cataloged from PDF version of thesis.Includes bibliographical references (p. 177-188).Large volumes of continuous waveform data are now collected in hospitals. These datasets provide an opportunity to advance medical care, by capturing rare or subtle phenomena associated with specific medical conditions, and by providing fresh insights into disease dynamics over long time scales. We describe how progress in medicine can be accelerated through the use of sophisticated computational methods for the structured analysis of large multi-patient, multi-signal datasets. We propose two new approaches, morphologic variability (MV) and physiological symbolic analysis, for the analysis of continuous long-term signals. MV studies subtle micro-level variations in the shape of physiological signals over long periods. These variations, which are often widely considered to be noise, can contain important information about the state of the underlying system. Symbolic analysis studies the macro-level information in signals by abstracting them into symbolic sequences. Converting continuous waveforms into symbolic sequences facilitates the development of efficient algorithms to discover high risk patterns and patients who are outliers in a population. We apply our methods to the clinical challenge of identifying patients at high risk of cardiovascular mortality (almost 30% of all deaths worldwide each year). When evaluated on ECG data from over 4,500 patients, high MV was strongly associated with both cardiovascular death and sudden cardiac death. MV was a better predictor of these events than other ECG-based metrics. Furthermore, these results were independent of information in echocardiography, clinical characteristics, and biomarkers.(cont.) Our symbolic analysis techniques also identified groups of patients exhibiting a varying risk of adverse outcomes. One group, with a particular set of symbolic characteristics, showed a 23 fold increased risk of death in the months following a mild heart attack, while another exhibited a 5 fold increased risk of future heart attacks.by Zeeshan Hassan Syed.Ph.D
