Age-, sex-, and ethnicity-stratified CMR strain reference ranges and centile-based categories from the Healthy Hearts Consortium
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: 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 2.5 th and 97.5 th 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.
Source: medRxiv
Authors: Janek Salatzki, Dorina-Gabriela Condurache, Roman Roy, Liliana Szabo, Leo Westbury, Tesfamariam Akilu, Ahmed M Salih, Sucharitha Chadalavada, Robin Bülow, Giovanni Donato Aquaro, Thu-Thao Le, Dominika Suchá, Nay Aung, Nicholas C. Harvey, Tim Leiner, Calvin W.L. Chin, Andrea Barison, Marcus Dörr, Matthias G. Friedrich, Florian Andre, Steffen E. Petersen, Zahra Raisi-Estabragh
Institutions: Queen Mary University of London, University Hospital Heidelberg, National Institute for Health and Care Research, William Harvey Research Institute, St Bartholomew's Hospital, Barts Health NHS Trust, Semmelweis University, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, MRC Lifecourse Epidemiology Unit, University of Southampton, University of Leicester, British Heart Foundation, Universitätsmedizin Greifswald, University of Pisa, National University of Singapore, Duke-NUS Medical School, National Heart Centre Singapore, University Medical Center Utrecht, Mayo Clinic, McGill University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Queen Mary University of London, Wellcome Trust, University Hospital Southampton NHS Foundation Trust, Deutsches Zentrum für Herz-Kreislaufforschung, Barts Charity, National Institute for Health and Care Research, British Heart Foundation, University of Southampton, European Commission, St George's University Hospitals NHS Foundation Trust, Barts Health NHS Trust, National Institute for Health Research Southampton Biomedical Research Centre, Medical Research Council
Awards: Programme 1: Musculoskeletal health in later life, G2475975703, G2930583843, An EU-Canada joint infrastructure for next-generation multi-Study Heart research, Programme 3: Early development and risk of adult musculoskeletal disease, G5264296147, G7054843324, G7782961643, G7816089160, G7953852530, G8470069120, G880270018, G8954186666, G976581334
OpenAlex ID: W7221649504