Cardiac Lymphatics Predict Survival After Heart Transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late allograft loss and a major factor limiting long-term survival after orthotopic heart transplantation (OHT). Cardiac lymphatics are severed at the time of donor heart explantation and not surgically reconstructed, potentially disrupting homeostatic processes. We examined whether variations in cardiac lymphatics could influence CAV and OHT outcomes by using endomyocardial biopsies. METHODS: The study is a single-center, blinded, retrospective case-control study using endomyocardial biopsies from 50 patients with primary OHT in the Emory Transplant Center (Atlanta, GA). Routine endomyocardial biopsies were obtained at 1 and 5 years after OHT, and angiograms were graded for CAV (no CAV(0), n=26; CAV(1), n=12; CAV(2-3), n=12). RESULTS: When the number of lymphatics/mm(2) was quantified in these patients, lymphatic area was found to be inversely correlated to CAV severity. Moreover, patients with lower lymphatic areas 1 year after OHT had higher mortality compared with their high lymphatic counterparts (n(low)=25; n(high)=25; 40% versus 12%, P=0.0196). CONCLUSIONS: These findings indicate a potential association between reduced lymphatics and CAV, where upon further validation lymphatic area might serve as a measurable parameter to identify patients at risk for CAV and mortality. Because the survival analysis included limited adjustments, additional studies will be needed to incorporate key clinical confounders capable of influencing the relationship between lymphatic development and OHT outcomes. Future studies should investigate the mechanistic link between cardiac lymphatics and CAV and if lymphangiogenic pathways have therapeutic potential to improve OHT outcomes.