Microvascular Resistance Reserve and Prognosis After Heart Transplantation

BACKGROUND Impaired microcirculatory function after heart transplantation is associated with increased risk for acute cellular rejection. Microvascular resistance reserve (MRR) is a novel index for assessing microcirculatory function, irrespective of epicardial coronary artery stenosis, but it has not been validated in transplanted hearts. OBJECTIVES The aim of this study was to investigate the prognostic impact of MRR in heart transplantation. METHODS The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. Coronary microcirculatory dysfunction was defined as MRR <= 3.0. Elevated microcirculatory resistance was defined as an index of microcirculatory resistance >= 15. The presence of epicardial coronary stenosis was assessed by fractional flow reserve. The primary outcome was a composite of death or biopsy-proven acute cellular rejection of grade >= 2R after transplantation. RESULTS Among the total patients, 22.1% (34 of 154) had impaired microcirculatory function (MRR <= 3.0), and 77.9% (122 of 154) had preserved microcirculatory function (MRR >3.0). During median follow-up of 730 days (Q1-Q3: 730-730 days), patients with MRR <= 3.0 showed increased risk for a composite of death or acute cellular rejection (adjusted HR: 5.31; 95% CI: 2.65-10.64; P < 0.001), acute cellular rejection (adjusted HR: 4.83; 95% CI: 2.20-10.60; P < 0.001), and death (adjusted HR: 5.19; 95% CI: 1.24-21.62; P 1/4 0.024). MRR was significantly associated with increased risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis (HR adjusted for fractional flow reserve: 1.89 per 1-U decrease in MRR; 95% CI: 1.46-2.46; P < 0.001) or elevated microcirculatory resistance (HR adjusted for index of microcirculatory resistance: 1.90 per 1-U decrease in MRR; 95% CI: 1.43-2.52; P < 0.001). CONCLUSIONS Impaired microcirculatory function, determined by MRR early after heart transplantation, identified patients at high risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis or elevated microcirculatory resistance. (Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731) (JACC Cardiovasc Interv. 2025;18:439-452) (c) 2025 by the American College of Cardiology Foundation.