The neutrophil to lymphocyte ratio in heart failure: a comprehensive review

Heart failure (HF) and systemic inflammation are interdependent processes that continuously potentiate each other. Distinct pathophysiological pathways are activated, resulting in increased neutrophil count and reduced lymphocyte numbers, making the neutrophil to lymphocyte ratio (NLR) a potential indirect marker of severity. We conducted this comprehensive review to characterize the role of NLR in HF.

We searched the PubMed (MEDLINE) database using the key words "neutrophil", "lymphocyte", "heart failure", "cardiomyopathy", "implantable cardioverter defibrillator", "cardiac resynchronization therapy" and "heart transplant".

We identified 241 publications. 31 were selected for this review, including 12,107 patients. NLR was correlated to HF severity expressed by clinical, biological, and imaging parameters, as well as to short and long-term prognosis. Most studies reported its survival predictive value. Elevated NLR (>2.1-7.6) was an independent predictor of in-hospital mortality [adjusted HR 1.13 (95% CI 1.01-1.27) - 2.8 (95% CI 1.43-5.53)] as well as long-term all-cause mortality [adjusted HR 1.43 (95% CI 1.1-1.85) - 2.403 (95% CI 1.076-5.704)]. Higher NLR levels also predicted poor functional capacity [NLR > 2.26/2.74, HR 3.93 (95% CI 1.02-15.12) / 3.085 (95% CI 1.52-6.26)], hospital readmissions [NLR > 2.9/7.6, HR 1.46 (95% CI 1.10-1.93) / 3.46 (95% CI 2.11-5.68)] cardiac resynchronization therapy efficacy [NLR > 3.45/unit increase, HR 12.22 (95% CI 2.16-69.05) / 1.51 (95% CI 1.01-2.24)] and appropriate implantable cardioverter defibrillator shocks (NLR > 2.93), as well as mortality after left ventricular assist device implantation [NLR > 4.4 / quartiles, HR 1.67 (95% CI 1.03-2.70) / 1.22 (95% CI 1.01-1.47)] or heart transplant (NLR > 2.41, HR 3.403 (95% CI 1.04-11.14)].

Increased NLR in HF patients can be a valuable auxiliary biomarker of severity, and most of all, of poor prognosis.