Background
Cardiac allograft vasculopathy (CAV), comprising coronary macro- and microvascular dysfunction, remains a major long-term complication following heart transplantation (HT) and is strongly associated with poor survival. The pathogenesis of CAV involves both immunologic and atherosclerotic risk factors. However, the specific role of type 2 diabetes mellitus (T2DM) in the development of microvascular CAV is not fully understood. While T2DM is known as an adverse prognostic factor after HT, the underlying pathomechanisms remain unclear. A better understanding of the relationship between T2DM and microvascular CAV could provide valuable insights into the pathogenesis of CAV and may help to improve patient management and outcomes.
Purpose
This study aims to evaluate the impact of T2DM on coronary microvascular function during routine CAV screening. We hypothesize that patients with T2DM exhibit impaired microvascular function compared to patients with normal glucose tolerance (NGT).
Methods
Between June 2025 and October 2025, 16 HT recipients underwent coronary angiography with intravascular ultrasound (IVUS) and additional microvascular function assessment as part of routine CAV surveillance. Exclusion criteria for microvascular testing were estimated glomerular filtration rate <30 ml/min, periprocedural radial artery spasm, and relevant coronary stenosis requiring intervention. Microvascular function was assessed using the bolus thermodilution technique with a pressure guidewire (PressureWire X, Abbott) at rest and during hyperemia induced by regadenoson. Analysis of microvascular function was performed using Coroflow software (Coroventis Research AB). Intimal thickness was determined by IVUS. Diagnosis of T2DM followed the criteria established by the American Diabetes Association.
Results
Of the 16 patients, 7 had T2DM, 3 met the criteria for prediabetes, and 6 patients had NGT. The mean time since HT was 64 months, and the mean age was 57 years. The mean coronary flow reserve (CFR) was 3.7 ± 2.2, and the mean index of microcirculatory resistance (IMR) was 15.1 ± 9.2. Applying standard cut-off values (CFR <2.5 or IMR >25), microvascular CAV was diagnosed in 5 patients, four of whom had T2DM. Univariate analysis revealed no statistically significant differences in CFR (Mean±SD: NGT 4.9±2.6, Prediabetes 2.7±1.2, T2DM 3.2±2.0; p = 0.268) or IMR (NGT 9.5±3.8, Prediabetes 22.7±4.6, T2DM 16.6±11.3; p = 0.101) among the diabetes status groups. HbA1c levels showed a significant positive correlation with IMR (r = 0.555, p = 0.026). Patients with T2DM exhibited significantly greater intimal thickness compared to patients with NGT (NGT 0.34±1.09, Prediabetes 0.4±0.1, T2DM 0.57±0.05; p = 0.01).
Conclusion
This study provides first evidence that impaired glycaemic control is associated with coronary microvascular dysfunction in HT recipients. The observed higher intimal thickness among patients with T2DM further suggests early involvement of the macrovasculature. T2DM emerges as a potentially relevant and modifiable risk factor for CAV, highlighting the importance of routine T2DM screening and stringent glycaemic management in the post-HT period to improve patient outcomes.
