Definition of Clinical and Immunological Phenotypes of Graft Dysfunction in Heart Transplant Recipients: Prognostic Implications and Role of Antibody Mediated Rejection

Background Despite its clinical relevance, there is a lack of consensus regarding the definition of graft dysfunction (GD) in heart transplant (HT). Herein we aim to characterize clinical phenotypes of patients with GD, either acute or chronic, comparing their outcomes with stable patients. In addition, we explored the risk factors outcomes in GD patients. Methods The patients were divided in 3 groups: Group A - Patients who recently underwent HT (<5 years); Group B - Patients with clinical and instrumental signs of GD, regardless of the distance of HT; Group C - Stable patients (HT > 5 years). Primary Endpoints were: overall mortality, hospitalizations for cardiovascular events and hospitalization for all-causes. The Combined Endpoints was death or /and hospitalizations for cardiovascular events (CV hospitalization). Results We enrolled 134 consecutive HT patients. Patients with GD 32(24%) had significant higher prevalence of class NYHA >II, low EF, CAV, longer QRS and Qtc on the ECG (p<0.01) and donor specific antibodies (DSA) (all p<0.05), as compared with group A and C. Clinical presentation was highly heterogeneous: 6(19%) had acute presentation, 3 for acute rejection, and 3 for acute coronary syndromes; 21(66%) had chronic presentation: 17(53%) associated with CAV, and 4(13%) as chronic dysfunction after antibody-mediated rejection. During the 2y follow-up, GD patients showed higher mortality (P=0.01) and higher CVE hospitalization rate (54; P< 0.01) than patients in group A and C. Low EF, time from HT, and chronic clinical presentation (p<0.01) were risk factors for the combined endpoint Conclusions GD after HT is characterized by highly variable clinical presentation and is correlated with a particularly poor prognosis. CAV is the most frequent etiology, and DSA are more often found in patients with GD than in stable ones, but do not seem to influence outcome.