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

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: cardiac allograft vasculopathy; cytomegalovirus; heart transplant; microvascular function; myocardial flow reserve.