Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation

Area of Science:

• Cardiology
• Transplantation Medicine
• Cardiovascular Physiology

Background:

• Acute cellular rejection is a significant cause of mortality and retransplantation in heart recipients.
• Coronary microcirculatory dysfunction is implicated in adverse transplant outcomes.

Purpose of the Study:

• To evaluate the prognostic value of the index of microcirculatory resistance (IMR) for predicting acute cellular rejection after heart transplantation.
• To assess the incremental prognostic value of IMR beyond established clinical factors.

Main Methods:

• Prospective enrollment of 154 heart transplant recipients 1 month post-transplant.
• Invasive coronary physiological assessment including IMR calculation under maximal hyperemia.
• Multivariable Cox regression and reclassification metrics (C-index, NRI, IDI) to analyze the association between IMR and biopsy-proven acute cellular rejection (grade ≥2R) over 2 years.

Main Results:

• Patients with acute cellular rejection had significantly higher IMR values at 1 month (23.1±8.6 vs. 16.8±11.1, P=0.002).
• IMR was significantly associated with acute cellular rejection risk (aHR per 5-U increase: 1.18; P=0.011).
• An IMR cutoff of ≥15 identified patients with a substantially higher risk (34.4% vs. 3.8%; aHR: 15.3; P<0.001) and improved risk prediction models.

Conclusions:

• Coronary microcirculatory dysfunction, assessed by IMR early post-transplant, is strongly associated with the risk of acute cellular rejection.
• IMR serves as a valuable clinical tool for early risk stratification of acute cellular rejection, complementing surveillance endomyocardial biopsies.