Diabetes worsens the adverse association between myocardial diffuse fibrosis and left ventricular strain
Authors: Chadalavada S , Rauseo E , Sanghvi M , Lee A M , Amir-Khalili A , Chirvasa M , Banik S , Fung K , Hann E , Piechnik S K , Neubauer S , Jensen M T , Aung N , Petersen S E 
Published: October 2024

Abstract

Background
Heart failure is a common cardiovascular complication to diabetes. Increased fibrosis of the myocardium has been suggested to be a mechanism, however, no convincing clinical evidence has so far been presented. A better understanding of how myocardial tissue characteristics influence functional aberration in diabetes could aid diagnosis, risk assessment and guide treatment. Native T1 is a CMR marker of diffuse fibrosis with diagnostic and prognostic value (1,2), and feature tracking (CMR-FT) strain is a sensitive measure of myocardial systolic function. In this study, we evaluated the association of CMR markers of fibrosis with markers of systolic function in individuals with and without diabetes.

Purpose
To understand the relationship between native T1 and myocardial strain and how diabetes may affect this.

Methods
Participants from the UK Biobank population imaging study were included. Left ventricular global longitudinal strain (GLS) was derived using a semi-automated batch processing software tool. Native T1 was derived from segmentation of the entire short axis slice using an automated quality control tool, excluding scans with predicted dice score of &lt;0.7. Multivariable linear models were used with the strain metrics as the outcome variable and native T1 and diabetes as the exposure variables. These models were adjusted for age, sex, BMI, ethnicity, smoking and alcohol status, prevalent hypertension hypercholesterolaemia and coronary artery disease. The effect of interaction between diabetes and native T1 on GLS was examined by introducing an interaction term.

Results
In total 41,533 participants were included, of which 1957 had diabetes – see Table 1 for baseline characteristics. The average GLS measured for those with diabetes was -17% and was -18% for those without. The average native T1 in those with diabetes was 935ms and 933ms for those without on the background of greater prevalence of cardiovascular risk factors in those with diabetes. In model adjusted for all relevant co-variates, individuals with diabetes had worse GLS measured compared to those without diabetes (β-coefficient: 0.51, p value &lt;0.001). Increasing fibrosis (native T1) was associated with worsening GLS (β-coefficient: 0.005, p value &lt;0.001) in all participants. However, in those with diabetes, increasing native T1 was associated with a greater decline in GLS compared to those without diabetes (interaction term β-coefficient: 0.005, p value &lt;0.001), with a relative impairment seen within normal ranges for native T1 - see Figure 1.

Conclusion(s)
This is the largest study of its kind to demonstrate a dose dependent relationship between increasing native T1, representing potential myocardial fibrosis, and myocardial strain, representing cardiac dysfunction. Our findings indicate that increased fibrosis alone does not explain the higher risk of HF in diabetes, other mechanisms, perhaps intracellular, might be at play.