Lymphopenia in the Adult Fontan Population: A Potential New Marker for Disease Assessment

Background Patients with complex congenital heart disease and Fontan palliation frequently develop extracardiac disease, including hematologic abnormalities such has lymphopenia, however the clinical implications of this finding are poorly understood and are therefore the topic of this investigation. Methods Fontan patients in our center (1999 - 2018) were evaluated for the presence and impact of lymphopenia. The cohort was divided into a lymphopenic (L) group (two consecutive absolute lymphocyte counts < 1*103 K/ μL) and never lymphopenic (NL) group. Clinical characteristics and hospital admissions (762 patient years) were evaluated. Results In 62 adult Fontan patients (34 ± 9 years old, women 32 (52%)), the earliest patients to develop lymphopenia did so 8 years after Fontan completion, with up to 60% of patients developing lymphopenia by 30 years. Lymphopenia was found to be associated with portal hypertension (VAST score NL: 0 (0-2) vs. L: 2 (0-4), p < 0.0001). A total of 76 heart failure and 81 arrhythmia-associated admissions occurred per 1,000 patient years. At 40 years post-Fontan, the probability of a heart failure admission was higher in the L group (L: 51 (86%) vs. NL: 8 (14%), p < 0.01). Conclusions Adult Fontan patients with lymphopenia demonstrated portal hypertension and lymphatic dysfunction more commonly, perhaps suggesting that this may be a marker of Fontan congestion and early Fontan failure. Further investigation into the relationship between lymphopenia, clinical outcomes, and Fontan function is needed.