The aim of the study by Doesch et al. was to investigate the prognostic value of cTNI-autoantibodies by enzyme-linked immunosorbent assay (ELISA), including 249 patients with DCM and 141 patients with ischemic cardiomyopathy (ICM). cTNI-autoantibodies (titer of ≥ 1:40) were detected in 18.7% of patients. In TNI-autoantibody positive patients mean left ventricular ejection fraction (LVEF) was 27.6 ± 5.8%, compared to 25.8 ± 5.9% in TNI-autoantibody negative patients, P = 0.03. The combined end-point of death (n = 118, 30.3% of total) or HTX (n = 44, 11.3% of total) was reached in 162 patients (41.5% of total). Kaplan–Meier analysis demonstrated superior survival (combined end-point of death or HTX in patients with DCM versus ICM (P = 0.0198) and TNI- autoantibody positive patients versus TNI-autoantibody negative patients (P = 0.0348). Further subgroup analysis revealed a favorable outcome in TNI-positive patients with DCM (P = 0.0334), whereas TNI-autoantibody status in patients with ICM was not associated with survival. In subsequent multivariate Weibull-analysis, a positive TNI serostatus was associated with a lower all-cause mortality in DCM patients (P = 0.0492), but not ICM. The authors conclude that this might indicate a prophylactic effect of TNI-autoantibodies in DCM.
Comments
The study by Doesch et al. apparently contrasts with most data published until now, showing detrimental effects of cTNI autoantibodies. There are explanations for this apparent discrepancy. Firstly, the number of autoantibody-positive patients (42 with DCM and 31 with ICM) was rather small for subgroup analysis of outcome. Association of negative autoantibody status with all-cause mortality was of borderline significance in multivariate analysis (p = 0.049). Secondly, at baseline the ICM group was older, had lower LVEF, lower VO2 max, a higher proportion of patients in NYHA class III-IV. Thus, it is likely to represent a more advanced heart failure cohort. In a prospective study by Caforio et al. AHA titers were reduced in end-stage DCM. Thus, DCM and ICM should be matched in terms of heart failure stage to detect potential differences in outcome related to autoantibody status. Thirdly, at least two epitopes of cTnI can induce myocardial damage in murine models. The exact binding site of the cTNI antibodies measured in the present study remains unclear, thus it may be that the cTNI detected by ELISA are not those that have been proven to be detrimental for cardiac myocytes in previous studies. Epitope mapping data on ELISA positive sera would be of interest.
Conclusion:
AHA data in the literature come from different groups and using different immunological detection methods; at present there are no correlative data on identical DCM and ICM cohorts at baseline and follow-up. An ongoing prospective multicenter multinational study, the ETiCs study has such design and should give relevant information on the functional and/or prognostic role of the major AHA specificities in DCM and ICM.
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