Chadalavada, Sucharitha

Abstract Background Myocardial feature-tracking (FT) strain from cardiovascular magnetic resonance (CMR) has incremental prognostic value beyond traditional imaging biomarkers. Clinical use is limited by the absence of population-specific healthy reference ranges. This study provides age-, sex-, and ethnicity-specific reference ranges for CMR-derived FT strain from the Healthy Hearts Consortium (HHC). Methods The HHC is an international collaboration comprising CMR scans from 9,088 verified healthy adults across six centres, covering the entire adult age spectrum and with diverse ethnic background. Standardised CMR acquisition protocols were used. Image analysis was performed by two experienced readers following pre-specified standard operating procedures and using two commercially available software platforms (cvi42®, Circle Cardiovascular Imaging Inc.; suiteHEART®, Neosoft LLC). The following metrics were extracted: i) global FT strain metrics from both ventricles (longitudinal, circumferential, and radial) and both atria (longitudinal); ii) strain rate; iii) Mitral/Tricuspid annular plane systolic excursion (MAPSE, TAPSE); iv) rapid strain (long-axis, junctional strain) from the left ventricle and both atria. Quality control included visual inspection of all images and the removal of biologically non-sensical values and extreme statistical outliers. Reference ranges were calculated by age group (deciles: 20-80 years), sex (male/female), and ethnicity (White, Black, Chinese, South Asian, Mixed/Other) using the 95% prediction interval method. Technical variations due to scanner vendor, software platform, and field strength (1.5T vs. 3.0T), were analysed. Results The study included 4,452 men (49%) and 4,636 women (51%). Ages ranged from 18 to 83 (mean 61±13) years. The sample included diverse ethnic backgrounds [White (81.7%), South Asian (5.6%), Mixed/Other (5.3%), Black (3.7%), and Chinese (3.7%)]. Women demonstrated significantly higher absolute strain values than men across. Absolute myocardial strain values were higher in younger age groups and lower in older age groups, most notably in left global circumferential and longitudinal strain. Ethnic differences in strain were most pronounced between White and Black as well as between White and Chinese individuals regarding left and right ventricular strain values, while left and right atrial strain values as well as rapid strain values, were similar across ethnic groups. Conclusion This study provides comprehensive, population-specific reference ranges for FT-CMR-derived myocardial strain, addressing a clinical knowledge gap. These findings inform clinical interpretation, improving diagnostic accuracy and risk stratification in different populations. This work represents a significant step towards a broader clinical implementation of myocardial strain analysis in routine cardiovascular care, ensuring more accurate classification of findings across varying demographic groups.

Abstract Background Myocardial strain derived from cardiovascular magnetic resonance (CMR) using feature tracking (FT) offers incremental prognostic value beyond traditional imaging markers. However, its broader clinical application is hindered by the lack of population-specific reference ranges. This study establishes age-, sex-, and ethnicity-specific normative data for FT-CMR-derived myocardial strain metrics from the Healthy Hearts Consortium (HHC). Methods The HHC is a large, international, multicohort initiative comprising CMR data from 9,088 rigorously screened healthy adults across six centers. The cohort spans the full adult age range and includes greater ethnic diversity than any comparable dataset. CMR scans were acquired using standardized protocols. Image analysis followed pre-specified standard operating procedures and was performed by two experienced readers using two commercial platforms (CVI42®, Circle Cardiovascular Imaging; suiteHEART®, Neosoft). Metrics extracted included: (i) global longitudinal, circumferential, and radial FT strain for both ventricles and atria; (ii) strain rate; (iii) annular plane systolic excursion (MAPSE, TAPSE); and (iv) rapid strain metrics (long-axis, junctional strain) for the left ventricle and atria. Comprehensive quality control involved visual review and exclusion of biologically implausible or extreme outlier values. Reference ranges were calculated using the 95% prediction interval method, stratified by age deciles (20–80 years), sex, and ethnicity (White, Black, Chinese, South Asian, Mixed/Other). The impact of technical factors—scanner vendor, field strength (1.5T vs 3.0T), and software platform—was also assessed. Results The study included 4,452 men (49%) and 4,636 women (51%), aged 18 to 83 years (mean 61 ± 13). The cohort was ethnically diverse: White (81.7%), South Asian (5.6%), Mixed/Other (5.3%), Black (3.7%), and Chinese (3.7%). Women consistently exhibited higher absolute strain values than men. A clear age-related decline in strain was observed, particularly in left ventricular global circumferential and longitudinal strain. Ethnic differences were most pronounced between White and Black, and White and Chinese individuals for RV and LV strain metrics; in contrast, RA, LA, and rapid strain metrics showed minimal ethnic variation. Conclusion This study delivers the most comprehensive age-, sex-, and ethnicity-specific reference ranges to date for FT-CMR-derived myocardial strain. These normative values support improved clinical interpretation, aiding diagnosis and risk stratification in diverse populations. The findings mark a pivotal advancement towards the routine integration of myocardial strain assessment in cardiovascular imaging practice.

ImportanceThe population prevalence of cardiac transthyretin amyloidosis (ATTR) caused by pathogenic variation in the TTR gene (vATTR) is unknown.ObjectiveTo estimate the population prevalence of disease-causing TTR variants and evaluate associated phenotypes and outcomes.Design, Setting, and ParticipantsThis population-based cohort study analyzed UK Biobank (UKB) participants with whole-exome sequencing, electrocardiogram, and cardiovascular magnetic resonance data. Participants were enrolled from 2006 to 2010, with a median follow-up of 12 (IQR, 11-13) years (cutoff date for the analysis, March 12, 2024). Sixty-two candidate TTR variants were extracted based on rarity (minor allele frequency ≤0.0001) and/or previously described associations with amyloidosis if more frequent.ExposureCarrier status for TTR variants.Main Outcomes and MeasuresAssociations of TTR carrier status with vATTR prevalence and cardiovascular imaging and electrocardiogram traits were explored using descriptive statistics. Associations between TTR carrier status and atrial fibrillation, conduction disease, heart failure, and all-cause mortality were evaluated using adjusted Cox proportional hazards models. Genotypic and diagnostic concordance was examined using International Statistical Classification of Diseases, Tenth Revision codes from the hospital record.ResultsThe overall cohort included 469 789 UKB participants (mean [SD] age, 56.5 [8.1] years; 54.2% female and 45.8% male). A likely pathogenic/pathogenic (LP/P) TTR variant was detected in 473 (0.1%) participants, with Val142Ile being the most prevalent (367 [77.6%]); 91 individuals (0.02%) were carriers of a variant of unknown significance . The overall prevalence of LP/P variants was 0.02% (105 of 444 243) in participants with European ancestry and 4.3% (321 of 7533) in participants with African ancestry. The LP/P variants were associated with higher left ventricular mass indexed to body surface area (β = 4.66; 95% CI, 1.87-7.44), and Val142Ile was associated with a longer PR interval (β = 18.34; 95% CI, 5.41-31.27). The LP/P carrier status was associated with a higher risk of heart failure (hazard ratio [HR], 2.68; 95% CI, 1.75-4.12) and conduction disease (HR, 1.88; 95% CI, 1.25-2.83). Higher all-cause mortality risk was observed for non-Val142Ile LP/P variants (HR, 1.98; 95% CI, 1.06-3.67). Thirteen participants (2.8%) with LP/P variants had diagnostic codes compatible with cardiac or neurologic amyloidosis. Variants of unknown significance were not associated with outcomes.Conclusions and RelevanceThis study found that approximately 1 in 1000 UKB participants were LP/P TTR variant carriers, exceeding previously reported prevalence. The findings emphasize the need for clinical vigilance in identifying individuals at risk of developing vATTR and associated poor outcomes.