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In this randomized, double-blind clinical study, we investigated the relationship between autoantibodies against cardiac troponin I (cTnI) and disease severity in elderly congestive heart failure (CHF) patients before and after titration of beta-blocker therapy.Anti-cTnI, cTnI, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in blood from 138 patients (73 ± 5.6 years, 48% male) with CHF in American Heart Association stages A–C were measured at baseline and after titration of beta-blockers to maximal tolerated dose. Median follow-up period was 85 days. Anti-cTnI was measured using an experimental assay (Abbott Diagnostics) and is expressed as a relative value unit (RVU) in relation to the mean value of a low-level control sample. Anti-cTnI values in CHF patients were also compared with measurements taken in a normal reference population of 300 healthy individuals (50% male). Cardiac troponin I and NT-proBNP levels were measured using routine assays (Architect® Abbott Diagnostics and Roche Diagnostics®). Median anti-cTnI was 0.53 and 0.56 RVU in healthy and CHF subjects, respectively (P = n.s.), and increased significantly to 0.67 RVU (P < 0.001) after beta-blocker titration. Mean cTnI values were 0.021 µg/L at baseline and fell significantly to 0.0046 µg/L at follow-up (P < 0.001). Median NT-proBNP values were 352 ng/L at baseline and 414 ng/L after titration (P = n.s.). In contrast to NT-proBNP and cTnI, anti-cTnI was not associated with the severity of CHF at baseline or follow-up.Levels of anti-cTnI tend to increase in elderly patients with CHF following titration of beta-blocker therapy but do not correlate with disease severity. Anti-cTnI is not a useful biomarker for heart failure diagnosis, prognosis, or monitoring. In contrast, levels of cTnI decreased following therapy and did correlate with disease severity.