Abstract
BackgroundSpontaneous T2DM in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. Myocardial deformation measurements have emerged as a superior way to measure left ventricular (LV) function in the early stage of cardiac dysfunction, making it possible to further evaluate early-stage LV dysfunction in spontaneous T2DM rhesus monkeys.MethodsSpontaneous T2DM rhesus monkeys with isolated diastolic dysfunction (T2DM-DD, n = 10) and corresponding nondiabetic healthy animals (ND, n = 9) were prospectively scanned for a CMR study. Circumferential and longitudinal peak systolic strain (Ecc, Ell), time to peak strain (tEcc, tEll) and peak diastolic strain rate (CSR, LSR) obtained from 2D/3D CMR-TT were compared with those obtained from CMR tagging separately. In addition, all CMR imaging protocols were performed twice in 9 ND animals to assess test-retest reproducibility.ResultsCompared with the ND group, the T2DM-DD monkeys demonstrated significantly impaired LV Ecc (− 10.63 ± 3.23 vs − 14.18 ± 3.19, p < 0.05), CSR (65.50 ± 14.48 vs 65.50 ± 14.48, p < 0.01), Ell (− 9.11 ± 2.59 vs − 14.17 ± 1.68, p < 0.05), and LSR (59.43 ± 19.17 vs 108.46 ± 22.33, p < 0.01) with the tagging. Only Ecc (− 13.10 ± 2.47 vs − 19.03 ± 3.69, p < 0.01) and CSR (148.90 ± 31.27 vs 202.00 ± 51.88, p < 0.01) were significantly reduced with 2D CMR-TT, and only Ecc (− 13.77 ± 1.98 vs − 17.26 ± 3.78, p < 0.05) was significantly reduced with 3D CMR-TT. Moreover, 2D/3D CMR-TT-derived Ecc and CSR correlated with the corresponding tagging values collectively, with a statistically significant ICC value (p < 0.05). Test-retest repeatability analysis showed that most tagging-derived biomarkers had acceptable repeatability (p < 0.01). In addition, 2D CMR-TT-derived indicators were poorer than those derived from the tagging method but better than those obtained using the 3D method, with larger ICCs except for tEcc (p < 0.05).ConclusionsLV systolic and diastolic deformations were impaired in spontaneous T2DM rhesus monkeys previously diagnosed with isolated diastolic dysfunction by echocardiography. The 2D CMR-TT-derived Ecc and CSR were effective in the evaluation of the myocardial systolic and diastolic functions of early-diabetic cardiomyopathy, with relatively higher test-retest reproducibility and acceptable correlation with the tagging method compared with the 3D CMR-TT method.
Highlights
Spontaneous type 2 diabetes mellitus (T2DM) in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans
These findings indicate an early stage of Diabetic cardiomyopathy (DCM) characterized by diastolic dysfunction with preserved left ventricular ejection fraction (LVEF) [6]
Agreement between 2D/3D cardiac MR (CMR)-TT and CMR tagging The absolute values of CMR tissue tracking (CMR-TT)-derived Peak systolic circumferential strain (Ecc) and Peak diastolic circumferential strain rate (CSR) in both the T2DM-diastolic dysfunction (DD) and ND groups were higher than the corresponding tagging values. Both CMR-TT 2D- and 3D-derived Ecc and CSR correlated with the corresponding tagging values, with statistically significant intraclass correlation coefficient (ICC) values (Ecc: 0.61 for 2D, 0.51 for 3D; CSR: 0.29 for 2D, 0.30 for 3D, p < 0.05) and a relatively narrow limit of agreement and a concentrated distribution in the Bland-Altman analysis (Figure 4)
Summary
Spontaneous T2DM in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. Sensitive diagnostic approaches in the early stage of DCM and novel strategies to reduce the risk of heart failure in diabetes patients are needed [3] Such approaches and strategies require the use of appropriate animals for preclinical and translational investigations. The changes in conventional echocardiography and cine magnetic resonance imaging (MRI) in spontaneous T2DM rhesus monkeys are similar to those found in humans with T2DM These findings indicate an early stage of DCM characterized by diastolic dysfunction with preserved left ventricular ejection fraction (LVEF) [6]. These spontaneous T2DM rhesus monkeys can be useful for preclinical and translational investigations in T2DM [7]
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