Combined Free Light Chains Are Novel Predictors of Prognosis in Heart Failure.
Jackson CE., Haig C., Welsh P., Dalzell JR., Tsorlalis IK., McConnachie A., Preiss D., McInnes IB., Sattar N., Petrie MC., Gardner RS., McMurray JJ.
OBJECTIVES: This study investigated the prevalence and potential incremental prognostic value of combined free light chains (cFLCs) in patients recently hospitalized with decompensated heart failure (HF). BACKGROUND: Inflammatory pathways are recognized in the pathogenesis and progression of HF. Free light chain (FLC) elevation is conventionally associated with monoclonal gammopathies, including multiple myeloma. Polyclonal increases in both kappa and lambda FLCs occur in autoimmune and other chronic inflammatory conditions. Recently, a novel assay for measuring kappa and lambda immunoglobulin FLCs together, known as combined free light chain (cFLC) has been developed. METHODS: Six hundred twenty-eight patients recently hospitalized with decompensated HF were studied. cFLCs were measured by turbidimetry using an immunoassay. The incremental prognostic value of cFLCs for mortality was evaluated using Cox proportional hazard models including 22 established predictors of outcome in HF. RESULTS: Of 628 patients, 290 (46%) died during a follow-up of 3.2 ± 1.5 years. Two hundred seventy patients (43%) had elevated cFLCs. There was a clear gradient in the risk of death according to cFLC quartile, with those in the top quartile having an unadjusted risk of mortality more than twice that of those in the lowest quartile (hazard ratio: 2.38; p < 0.0001). After multivariable analysis, cFLC remained an independent predictor of mortality, with an almost 50% higher adjusted risk for those in the top compared with bottom quartile. Older age, lower body mass index, New York Heart Association classification III/IV, previous myocardial infarction, current smoking and B-type natriuretic peptide, bilirubin, high-sensitivity C-reactive protein, glycated hemoglobin, and lymphocyte concentrations were also independent predictors of mortality. CONCLUSIONS: cFLCs are an independent predictor of mortality in patients recently hospitalized with decompensated HF. Further work is required to assess the effects of HF therapies on cFLC concentrations and whether or not directly targeting this marker of inflammation improves prognosis for patients with HF.