MRI in Diabetic Cardiomyopathy

Corresponding Author

Patients with diabetes are at an increased risk of developing cardiovascular disease, with heart failure (HF) being an underappreciated complication, often manifesting as the initial presentation of cardiovascular disease.¹ Data from the Framingham Heart Study showed a 2- to 5-fold increase of HF among patients with diabetes.² Furthermore, diabetic cardiomyopathy has long been recognized as a possible cause of heart failure with preserved ejection fraction (HFpEF), although detailed mechanisms can be diverse and complex. An intermediate clinical stage (as stage B HF, or pre-HF) featured by abnormal myocardial structure or functional disturbances may occur in the transition from at-risk stage (as stage A HF) to overt HF development (as stage C HF).³ Diabetic cardiomyopathy in such a pre-HF stage typically represents a disease entity characterized by elicited myocardial fibrosis, stiffness, and hypertrophy with dysglycemia as the primary etiology independent of other risk factors including obesity, coronary artery disease, hypertension, or coexisting valvular heart disease.⁴ The pathophysiology underlying diabetic cardiomyopathy may involve complex interactions between numerous pathways, such as the activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, oxidative stress, altered intracellular calcium homeostasis, increased formation of advanced glycation end products, and alterations in myocardial energy substrates.^1,4 Additionally, the period during which early functional and structural changes in the pre-HF stage of diabetic cardiomyopathy is rather prolonged.

Recent advances in imaging myocardial deformations have emerged as a powerful tool to provide additional information beyond traditional volume estimates and left ventricular ejection fraction (LVEF).⁵ More importantly, these measures are capable of identifying early impairment of myocardial contractile function even while the LVEF is relatively preserved.⁵ By combining further measurements of the speed of deformation (strain rate), subtle disturbances in both global and regional systolic and diastolic functions can be obtained. With advancements in cardiac magnetic resonance imaging (MRI), comprehensive measures of myocardial tissue characterization are feasible, which may allow us to capture insights into the delineation and staging of cardiomyopathy before an overt structural anomaly develops.⁶ This is particularly relevant in the clinical application of HFpEF, a syndrome with diverse etiologies that impair myocardial performance while maintaining global left ventricular (LV) pump function.

In this issue of JACC: Asia, Yang et al⁷ report a study in which they prospectively enrolled 475 consecutive patients with diabetes who presented at different stages of HF with preserved LVEF in China.⁷ Additionally, 78 healthy volunteers were recruited as controls. Using comprehensive cardiac MRI analysis, the investigators studied cardiac structural and functional (strain and strain rate measure) changes across 4 groups: healthy controls and diabetic participants across different HF stages (A-C). The global extracellular volume (ECV) fraction derived from the pre- and post-gadolinium contrast MRI analyses was used to represent the amount of interstitial fibrosis within the myocardium. Late gadolinium enhancement was excluded from ECV calculations in this study. Despite certain inherent limitations such as single-center enrollment, observational design, missing echocardiography or incomplete contrast-enhanced MRI or T1 mapping in some participants and lack of outcomes during follow-up, the study provides valuable insights into the use of advanced MRI technology for improved tissue characterization in diabetic cardiomyopathy.

Yang et al⁷ report that global early diastolic longitudinal strain rate, as measured by MRI, significantly distinguished diabetic individuals in stage A HF from healthy controls (0.66 ± 0.19/s vs 0.81 ± 0.17/s; area under the receiver operating characteristic curve: 0.726; cutoff: 0.623/s) and remained an independent predictor even after multivariable adjustment, albeit not statistically different between stage B and C HF groups. In contrast, global longitudinal strain (GLS), systolic strain rate, and ECV showed progressive and significant deterioration from stages A (at risk) and B (pre-HF) to stage C HF. Both GLS (OR: 1.33; 95% CI: 1.04-1.71; cutoff: –14.6%) and ECV (OR: 1.30; 95% CI: 1.06-1.59; 26.48%) were independent indicators distinguishing stage B from stage A HF. Overall, these findings suggest that early diastolic deformational parameters were particularly useful in differentiating patients with stage A HF from healthy controls, whereas GLS and ECV measurements continued to show differences in the later stages of HF among diabetic individuals (Figure 1). Interestingly, most MRI-based parameters showed significant alterations with increasing comorbidities. Notably, the diabetic participants classified into the stage C HF group in the current study were much younger compared to those in another prospectively enrolled multiregion registry (Asian-HF)⁸ and presented with significantly higher LV chamber size and worse LVEF compared to the normal control and stage A-B HF groups. Whether the observed declines of LVEF and significant expansion of LV size in stage C HF group represent a unique HFpEF phenotype in the current study or manifest as universal findings in such a population and are replicable to other cohort remains to be determined in the future.

Figure 1.

Comparison of Magnetic Resonance Imaging–Derived Measurements Between Heart Failure Stages

Comparisons of cardiac magnetic resonance imaging (MRI)-derived measurements between different heart failure (HF) stages (A to C) in diabetic cardiomyopathy and control subjects. Stage A represent at risk of HF, Stage B represent pre-HF and Stage C represent HF subjects. ∗Note: all participants had preserved (≥50%) LVEF in this study. ECV = extracellular volume fraction; eGLSR = global early diastolic longitudinal strain rate; GLS = global longitudinal strain; LAVi = left atrial volume index; LVEF = left ventricle ejection fraction; LVMi = left ventricle mass index; sGLSR = global systolic longitudinal strain rate.

Despite a remarkable deterioration of GLS (–11.6% ± 3.3%) and significant decline of LVEF observed in stage C HF group, the numerical differences in ECV values between stage B-C and other groups were relatively small, with some overlap when accounting for the standard deviation (30.5% ± 4.1% in stage C vs 29.1% ± 3.5% and 27.0% ± 2.9% in stage B and A, respectively). The elevated ECV in stage C likely reflects the greater interstitial fibrosis burden from a more advanced HF stage where the global pump function becomes impaired. Furthermore, several traditional geometric markers, including the left atrial volume index and LV mass index, also showed statistical differences in stage B compared to the control and stage A HF groups. Taken collectively, these findings likely limit the clinical applicability of precise staging of diabetic cardiomyopathy using ECV alone in practical use. Therefore, real-world implementation and the true additive value of using such an index to discriminate diabetic individuals into different HF stages in clinical practice may need to be validated in larger future cohorts. As Yang et al⁷ mention, another important issue is that certain novel medications used (eg, sodium-glucose cotransporter-2 inhibitors) have been shown to exert cardioprotective effects by reversing LV remodeling and enhancing GLS as a potential confounder to these measures.⁹ However, these effects did not appear to influence outcomes in the current study models.

Nonetheless, the investigators should be commended for their efforts and success, as this study represents the largest ethnic Asian cohort to date comparing comprehensive MRI measures between healthy individuals and patients with diabetes at different HF stages. These data support the role of MRI as a clinical imaging modality capable of providing additional information about myocardial textures and function beyond structural remodeling in a relatively preserved LVEF. Careful cardiac imaging in the pre-HF phase to early identify structural or functional anomaly and myocardial fibrosis is crucial in the clinical management of patients with diabetes where appropriate intervention may halt the progression into clinical HF. The incremental value of ECV measurement as a surrogate marker imaging interstitial myocardial fibrosis to better characterize diabetic cardiomyopathy at an earlier stage may warrant future studies.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.