Cytomegalovirus infection is associated with impaired myocardial flow reserve after heart transplantation

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation (HT). This study evaluates the relationship between clinically significant cytomegalovirus infection (CS-CMVi) and CAV using cardiac positron emission tomography (PET).We retrospectively evaluated HT patients from 2005 to 2019 who underwent cardiac PET for CAV evaluation. Multivariable linear and logistic regression models were used to evaluate the association between CS-CMVi and myocardial flow reserve (MFR). Kaplan-Meier and Cox regression analyses were used to assess the relationship between CS-CMV, MFR, and clinical outcomes.Thirty-two (31.1%) of 103 HT patients developed CS-CMVi at a median 9 months after HT. Patients with CS-CMVi had a significantly lower MFR at year 1 and 3, driven by reduction in stress myocardial blood flow. Patients with CS-CMVi had a faster rate of decline in MFR compared to those without infection (-0.10 vs -0.06 per year, p < 0.001). CS-CMVi was an independent predictor of abnormal MFR (<2.0) (odds ratio: 3.8, 95% confidence intervals (CI): 1.4-10.7, p = 0.001) and a lower MFR (β = -0.39, 95% CI: -0.63 to -0.16, p = 0.001) at year 3. In adjusted survival analyses, both abnormal MFR (log-rank p < 0.001; hazard ratio [HR]: 5.7, 95% CI: 4.2-7.2) and CS-CMVi (log-rank p = 0.028; HR: 3.3, 95% CI: 1.8-4.8) were significant predictors of the primary outcome of all-cause mortality, retransplantation, heart failure hospitalization, and acute coronary syndrome.CS-CMVi is an independent predictor of reduced MFR following HT. These findings suggest that CMV infection is an important risk factor in the development and progression of CAV.