Pathology-based anatomical assessment and physiological evaluation using coronary flow reserve and index of microcirculatory resistance in microvascular coronary allograft vasculopathy

Background Microvascular involvement in cardiac allograft vasculopathy (CAV) can occur even without angiographic epicardial lesions and is associated with adverse outcomes. Structural abnormalities are assessed by endomyocardial biopsy, whereas physiological evaluation is performed using invasive indices such as coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). However, same-session links between biopsy-defined microvasculopathy and invasive physiology remain limited. Purpose To examine the association between biopsy-defined microvasculopathy and invasive coronary physiological indices in heart transplant recipients without haemodynamically significant epicardial disease. Methods We retrospectively analysed consecutive recipients undergoing routine surveillance catheterisation with same-session endomyocardial biopsy and invasive physiology (CoroFlow; LAD in all patients). Microvessels (10–20 μm) were graded using a semi-quantitative histological rubric (A–D); grades C/D were defined as pathology-positive microvasculopathy (pMVS+). Percent area stenosis was quantified morphometrically. Group comparisons used Mann–Whitney U tests; associations were assessed using Spearman’s rank correlation. Results Sixteen recipients were included. CFR was significantly lower in pMVS+ than pMVS− (1.7 [1.35–2.2] vs 2.5 [2.2–4.5]; P=0.0126), whereas IMR did not differ (20 [12–27] vs 15 [14–16]; P=0.337). As an exploratory component analysis, resting transit time was shorter in pMVS+ (Tmn_rest 0.38 [0.25–0.71] vs 0.86 [0.59–1.91]; P=0.026), while Tmn_hyper was similar (P=0.425), suggesting a resting-flow contribution to reduced CFR. Pathological grade correlated inversely with CFR (Spearman ρ=−0.51; P=0.045), whereas percent area stenosis showed no significant association with CFR or IMR. Conclusion In a same-session biopsy–physiology pilot study, biopsy-defined microvasculopathy was associated with impaired flow reserve (CFR) without a parallel change in IMR. An integrated histological grade aligned with CFR better than geometric stenosis, supporting CFR as a potential functional correlate of transplant microvasculopathy. These findings may support risk stratification and surveillance strategies and could, in the future, reduce reliance on repeated endomyocardial biopsy.Figure1Figure2