Age-, sex-, and ethnicity-stratified CMR strain reference ranges and centile-based categories from the Healthy Hearts Consortium

Background This study presents reference ranges for cardiovascular magnetic resonance (CMR)-derived myocardial strain from the Healthy Hearts Consortium, while evaluating variations by demographic characteristics (age, sex, and ethnicity) and technical factors (scanner vendor, magnetic field strength). We derived reference ranges and centile-based categories for ventricular, atrial, and rapid strain parameters. The prognostic relevance of these categories was assessed by examining their associations with incident cardiovascular events. Methods The dataset included 9,088 CMR studies. Automated image analysis pipelines were established using suiteHEART (NeoSoft Inc.) and cvi42 (Circle Cardiovascular Imaging). A three-step quality control framework was applied including exclusion of incomplete data, visual assessment of image and segmentation quality, and statistical outlier removal. Ventricular strain and strain rate were measured using both software solutions. Additional cvi42 derived metrics included velocity and displacement, annular plane systolic excursion metrics, and rapid strain parameters. Age- and sex-specific reference ranges were generated using lambda-mu-sigma (LMS) modeling with penalized splines. Reference ranges were defined as values between the 2.5th and 97.5th percentiles. For lower-tail classification, values below the 2.5th percentile were considered mildly out-of-range and values below the 0.5th percentile at least moderately out-of-range. Differences across scanner vendors (Siemens, Philips, GE) and magnetic field strengths (1.5 T vs. 3 T) were evaluated using adjusted linear models. The prognostic relevance of selected cvi42-derived categories was evaluated in approximately 45,000 UK Biobank participants using Cox regression adjusted for age, sex, and body mass index. Results After quality control, 8,975 CMR examinations (cvi42) and 8,992 (suiteHEART) were available for analysis; these represent software-specific analytic cohorts. Most exclusions occurred during visual quality control. Women had higher absolute ventricular and atrial strain values than men across all age groups. Left ventricular (LV) longitudinal strain and strain rate were slightly lower in older ages, whereas circumferential and radial parameters remained largely stable. Left atrial strain was also lower in older age groups, while right atrial strain did not vary by age. Annular plane systolic excursion and rapid strain metrics showed similar sex-specific patterns, with modestly lower atrial and displacement values in older groups. Ethnicity-related differences were modest, heterogeneous, and substantially smaller in magnitude than age- and sex-related differences. Technical effects were parameter specific. While LV longitudinal and circumferential strains were largely unaffected, radial strain was higher at 3 T and showed vendor-related differences. LMS-derived reference ranges and centile thresholds were applied both across all ethnicities and within ethnicity-specific analyses, and are presented stratified by age and sex. In the prognostic analysis, centile categories were most consistently associated with incident heart failure. LV longitudinal, circumferential, and radial strain below the 0.5th centile were associated with significantly increased risk of incident heart failure (HRs: 9.9 to 12.4, 95% CIs 7.00-13.90 to 8.49-18.06). Conclusion This study provides age- and sex-specific reference ranges and centile-based categories for CMR-derived strain parameters in a large reference population. Age and sex represent the primary determinants of myocardial deformation, whereas scanner-related effects are parameter-specific. Values in the lower extremes of the healthy reference distribution, particularly for LV strain, are associated with increased risk of incident heart failure. These findings enable standardized, centile-based classification of myocardial strain, facilitating consistent interpretation and improving risk stratification in research and clinical practice.