Proteomic profiling to identify prognostic biomarkers in heart failure.

BACKGROUND The ability to predict mode, as well as risk, of death in left ventricular systolic dysfunction (LVSD) is important, as the clinical and cost-effectiveness of implantable cardioverter defibrillators (ICD) therapy depends on its use in appropriately selected patient populations. The value of a proteomic approach in identifying prognostic biomarkers in LVSD is unknown. The aims of this pilot study were to use proteomic techniques to identify serum biomarkers associated with LVSD and to prospectively explore their association with prognosis. PATIENTS AND METHODS Serum was analysed by surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) in patients with (n=78) and without (n=45) systolic heart failure (SHF). Spectra were compared to identify differentially expressed signal peaks as potential biomarker indicators. The ability of these peaks to predict all-cause mortality and survival with appropriate ICD therapy was then tested prospectively in patients with ICDs, on the background of LVSD (n=141). RESULTS For the identification stage spectra (2-200 kDa) from SHF and control patients were randomly separated into two equally sized discovery and validation sets. Six protein peaks were identified that were differentially expressed in SHF in both sets. In the prospective phase, during a mean follow-up of 15±3 months, 11 patients died and 39 survived with appropriate ICD therapy. Five out of the six proteomic biomarkers predicted all-cause mortality but none predicted appropriate ICD therapy. CONCLUSION These results provide proof-of-principle and are supportive of the SELDI proteomic approach as a high-throughput screening tool in identifying potentially prognostic protein peaks in patients with LVSD.