Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction

Background The utility of ventricular asymmetry as an imaging biomarker for cardiovascular risk has not been assessed in population cohorts. Objectives This study presents a comprehensive assessment of the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases. Methods Cardiovascular magnetic resonance (CMR) imaging metrics derived from automated image analysis were examined, along with clinical outcomes ascertained through linked health records. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV, RV) end-diastolic volumes. The normal range for ventricular symmetry was defined in a healthy subset without cardiorespiratory disease. Participants with values outside the 5 th -95 th percentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures. Results The analysis includes 44,796 participants (average age 64.1±7.7 years; 51.9% women). Ventricular asymmetry, in either direction, was associated with older age and adverse cardiovascular remodeling. LV-dominance was linked to an array of pre-existing vascular risk factors and cardiovascular diseases, and a two-fold increased risk of incident heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an elevated risk of all-cause mortality. Conclusions Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics. Condensed abstract Healthy hearts have a predictable symmetry. Asymmetry produced when one, e.g. the left ventricular (LV) volume outweighs the right, or vice versa, could be an important indicator of underlying disorders, and powerful risk indicator for future disease. In this study of 44,796 UK Biobank participants, we show that LV dominance associates significantly with clinical risk factors, existing heart disease, and a two-fold increased risk for future heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an increased risk of all-cause mortality. Ventricular asymmetry is easily calculated from conventional imaging metrics and could be a highly useful addition to the clinician’s toolkit.