Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction <50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.