A Novel Application of the Interferon-Gamma Release Assay (IGRA) among End-Stage Heart Failure Patients Awaiting Heart Transplantation

Interferon-gamma release assays (IGRAs) measure immune responses to pathogen-specific antigens such as tuberculosis. However, the assay hinges on a functional immune system. Whether IGRAs can be used to identify heart transplant candidates with impaired immunity and worse prognosis is not known. From August 1st, 2014 to August 31st, 2018, all heart transplant candidates at a medical center in Taiwan who received an IGRA (QuantiFERON®-TB Gold In-Tube) during transplant evaluation to screen for latent tuberculosis infection were included. Inadequate immunity was defined as a response of <1 IU/ml of interferon-γ (IFN-γ) to the common mitogen in the positive control tube of the IGRA. Patients were followed until death or January 31st, 2019 for all-cause mortality and subsequent infections. A total of 103 patients were included, and 23 (22.3 %) had inadequate mitogen responses. After a median follow-up duration of 676 days (interquartile range [IQR] 387-1299), 34 (33.0 %) patients received a heart transplant and 23 (22.3 %) patients died. Forty-eight (46.6 %) patients developed infections, predominantly bacteremia (37.5 %). Those with inadequate mitogen responses had significantly higher rates of mortality (39.1 % vs. 17.5 %, p = 0.028) and infections (65.2 % vs. 41.3 %, p = 0.042). In the multivariate analysis, inadequate responses to mitogen were significantly associated with mortality and infections (hazard ratio [HR] 3.36, confidence interval [CI] 1.22-9.23, p = 0.019; HR 2.75, CI 1.18-6.40, p = 0.019). Patients with heart failure and inadequate mitogen responses by IGRAs had a higher risk of mortality and infection. IGRAs may have a novel application in prognostication of heart transplant candidates.