Predictive value of low relative lymphocyte count in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial.

BACKGROUND Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF. METHODS AND RESULTS We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction ≤40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months. The primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization were analyzed in patients with available baseline complete blood counts (n=3717). Lymphocyte percentage was analyzed as a continuous variable. Times to events were compared using log-rank tests and multivariable Cox regression models. Patients with low lymphocyte percentage tended to be older and had higher rates of comorbid disease (diabetes mellitus, atrial fibrillation, and renal insufficiency). Low lymphocyte counts were associated with wide QRS duration, high natriuretic peptides, and low ejection fraction, blood pressure, and serum sodium. These patients were less likely to receive evidence-based HF medications. After adjusting for 22 known clinical risk factors, a 10% decrease in lymphocytes was associated with an increased hazard of all-cause mortality (adjusted hazard ratio 1.31 [95% CI: 1.14-1.150], P<0.001) and cardiovascular mortality or HF hospitalization (adjusted hazard ratio 1.14 [95% CI: 1.04-1.25], P=0.007) in the first 100 days postdischarge. Lymphopenia during hospitalization normalizes in majority of patients in the early postdischarge period. CONCLUSIONS Low relative lymphocyte count during hospitalization for HF is an independent predictor of poor outcomes in the early postdischarge period, beyond traditional prognostic indicators.