Cardiometabolic myocardial remodelling across the glycaemic spectrum: a multi-level meta-analysis of CMR T1 mapping and extracellular volume
A Dharan, S Poon, F Takeuchi, J Greenwood, Taylor A, J Hare, E Levelt, S GutmanAbstract
Background
Diabetes mellitus confers a 2–5-fold higher risk of heart failure, yet the tissue-level substrate linking chronic hyperglycaemia to myocardial injury remains incompletely defined.1 Cardiovascular magnetic resonance (CMR) T1 mapping and extracellular volume (ECV) quantify diffuse interstitial fibrosis non-invasively, but their behaviour across normoglycaemia, prediabetes,2 type 1 and type 2 diabetes, and their quantitative relationship with HbA1c, remain uncertain.
Purpose
To characterise diffuse myocardial fibrosis and early ventricular remodelling across the glycaemic spectrum, and to quantify their association with HbA1c using CMR tissue mapping.
Methods
We conducted a PRISMA-guided systematic review and meta-analysis of adult cohorts undergoing CMR T1/ECV mapping with glycaemic stratification. Twenty-two studies (4,708 participants) contributed 28 ECV and 27 native T1 contrasts. Three-level random-effects models (restricted maximum likelihood) were used as primary analyses to account for clustering of contrasts within studies. Hartung–Knapp two-level models, cluster-robust variance estimation, and Bayesian random-effects models were prespecified sensitivity analyses to assess robustness. Moderator analyses evaluated technical (field strength, mapping sequence, region-of-interest, haematocrit correction) and clinical (diabetes type) sources of heterogeneity, and multilevel meta-regression assessed associations between mean cohort HbA1c and fibrosis indices.
Results
Compared with normoglycaemia, prediabetes and diabetes were associated with higher ECV (three-level SMD 0.78, 95% CI 0.48–1.07) and native T1 (SMD 0.43, 95% CI 0.20–0.66), with substantial residual heterogeneity (I² >70%) that did not materially alter effect magnitude across modelling approaches. Global longitudinal strain was impaired (SMD 0.67, 95% CI 0.38–0.95) and left-ventricular mass index increased (SMD 0.34, 95% CI 0.10–0.58), consistent with early structural and functional remodelling. Each 1% higher HbA1c corresponded to 0.35 SD higher ECV and 0.19 SD higher native T1, although slopes were statistically imprecise after accounting for clustering and between-study variability. Effects were directionally consistent across technical subgroups and most pronounced in overt type 2 diabetes.
Conclusions
CMR-derived ECV and native T1 identify a diffuse fibrosis phenotype that scales with glycaemic burden and parallels early ventricular remodelling. These findings reinforce chronic hyperglycaemia as a mechanistic driver of heart failure–relevant myocardial injury and support CMR tissue mapping as a robust imaging biomarker and candidate surrogate endpoint for cardiometabolic trials.