Myocardial Strain May Reflect Advanced Graft Injury Rather Than Acute Rejection After Heart Transplantation

Aims Cardiac magnetic resonance imaging (CMR) T1 and T2 mapping accurately detect acute heart transplant rejection, but the diagnostic value of CMR-derived strain imaging remains uncertain, particularly for right ventricular strain. Data incorporating donor-derived cell-free DNA (dd-cfDNA) into a composite reference standard are limited. We evaluated the diagnostic accuracy of CMR-derived left and right ventricular strain and ejection fraction for detecting acute rejection in pediatric and adult heart transplant recipients. Methods and results Blinded analysis of 1.5T CMR studies was performed in pediatric and adult heart transplant recipients 1–24 months post-transplant and during five additional rejection episodes 3–14 years post-transplant. Left and right ventricular strain and ejection fraction were quantified using semi-automated post-processing. Acute rejection was defined using a composite reference standard comprising endomyocardial biopsy (EMB), clinical assessment, and dd-cfDNA. Diagnostic performance was assessed using cut-offs from receiver operator characteristic analysis. Among 214 CMR studies in 58 patients, 13 cases of acute rejection were identified. Diagnostic performance for detecting acute rejection was highest for pediatric right ventricular longitudinal strain (AUC 0.782, 95% CI 0.565–0.999), although imprecise due to data heterogeneity. All other cardiac functional parameters demonstrated limited discrimination in both pediatric and adult patients (AUC 0.536–0.739). Models based on individual rejection indicators (EMB, clinical assessment, and dd-cfDNA) also showed poor diagnostic accuracy. Conclusion CMR-derived strain and ejection fraction showed limited diagnostic value for detecting acute rejection. Routine strain analysis therefore appears to have limited utility for rejection surveillance, with abnormalities primarily reflecting more advanced graft injury.