Literature review: Assessing heterogeneity on cardiovascular magnetic resonance imaging- a novel approach to diagnosis and risk stratification in cardiac diseases.

Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy (HCM), replacement fibrosis with akinesia in an infarct-related coronary artery territory and pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance imaging (CMR) mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate earlier diagnosis, better risk stratification and more comprehensive prediction of treatment response. Small cohort and case-control studies demonstrate feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential and radial function across the myocardium. Two of the most promising heterogeneity measures are mean absolute deviation of regional standard deviations (madSD) on native T1 and T2 and the SD of time to maximum regional radial wall motion, termed tissue synchronisation index (TSI) in a 16-segment LV model. Real world limitations include the non-standardisation of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small inadequately powered patient samples. We therefore propose a 3-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies and finally, comprehensive internal and external validation.