Endogen microvascular dysfunction is associated with worse outcomes in heart transplantation

Abstract Background Cardiac allograft vasculopathy (CAV) affects the health of both epicardial and microvascular blood vessels in heart transplants. Coronary microvascular dysfunction (CMD) has been associated with poor outcomes in the non-transplant population. Two patterns of microvascular dysfunction have been characterized, classical (low stress flow) and endogen (high rest flow). Whether these patterns of microvascular dysfunction are associated with outcomes in the transplant population has not been thoroughly evaluated. Purpose The purpose of the study was to assess the relationship between microvascular dysfunction and adverse outcomes in patients with heart transplants. Methods Patients with no history of angiographic CAV who underwent positron emission tomography myocardial perfusion imaging and were found to have normal perfusion (summed stress score = 0) were included in the study. Patients were then classified by microvascular dysfunction: normal (flow reserve ≥ 2.0) versus abnormal (flow reserve <2.0). Patients were further subclassified based on pattern of microvascular dysfunction, classical (stress myocardial flow <1.7 mL/min/g) and endogen (stress myocardial flow ≥1.7 mL/min/g). The two primary outcomes were all-cause mortality and a composite of death, heart failure hospitalization, acute coronary syndrome, and revascularization. Kaplan-Meier survival and Cox proportional regression were used to assess the relationship between microvascular function and outcomes. Results In total, 359 patients were enrolled in the study, of which 29 (8%) had classical CMD and 78 (22%) had endogen CMD. Patients with endogen CMD were more likely to be women (46%) compared to 31% for normal microvascular function and 24% for classical CMD. During a median follow up period of 2.0 years (Q1 1.7, Q3 2.3), 36 patients had an adverse event and 19 patients died. Endogen CMD was associated with a significantly higher risk of both the composite outcome, HR 2.30 (1.15 – 4.61), and all-cause mortality, 4.19 (1.64 – 10.73). Classical CMD was not associated with either the composite outcome, HR 0.88 (0.20 – 3.84) or death, HR 1.02 (0.12 – 8.33), however assessment of classical CMD was limited by small sample size. Conclusions Endogen-type CMD is associated with worse intermediate-term outcomes in transplant patients compared to normal microvascular function and classical-type CMD, although comparison to classical-type CMD was limited by small sample size.Table 1:DemographicsFigure 1:KM Survival Curves