Assistant Professor University of Ottawa Heart Institute University of Ottawa Heart Institute Ottawa, Ontario, Canada
Background: Serum troponins are a marker of cardiac involvement in patients with Fabry disease. Persistently elevated troponin levels may also result from macrotroponins, which are complexes formed by the binding of autoantibodies to circulating troponins. This study aimed to evaluate the association between left ventricular (LV) mass and late gadolinium enhancement (LGE) with serum troponin levels in patients with Fabry disease, before and after accounting for the presence of macrotroponins.
METHODS AND RESULTS: Single-centre cross-sectional analysis of 77 consecutive patients with Fabry disease undergoing cardiac MRI. Patients with routine serum high-sensitive cardiac troponin I values three times above the 99% percentile were evaluated for the presence of macrotroponin, which was defined as a reduction of ≥60% in the troponin I levels post-IgG removal using protein G resin. The association between LV mass and LGE with serum troponin levels was evaluated in all patients, before and after correcting troponin values for macrotroponins (i.e. before and after IgG removal). Statistical analyses included sex- and age-adjusted robust MM estimation and logistic regression. The median age was 50 (IQR:38 to 63) years and 53 (68.8%) were female. Macrotroponins were detected in 9 (11.7%) patients (Table). The median troponin level was 4.5 (2.0 to 21.5) ng/L in patients without macrotroponins, 928 (411 to 1435) ng/L in patients with macrotroponins before IgG removal and 6 (2 to 37) ng/L in the overall population. After IgG removal, the median residual troponin value was 19.2 (13.2 to 22) ng/L in patients with macrotroponins and 6 (2 to 22) ng/L in the overall population. When analyzing patients without macrotroponins and patients with macrotroponins before IgG removal, no significant associations were observed between troponin levels and either LV mass (β-coefficient 0.01; 95%CI: 0.00 to 0.02; p=0.134) or LGE presence (OR 1.00; 95%CI: 0.99 to 1.00; p=0.164). When analyzing patients without macrotroponins and patients with macrotroponins after IgG removal, each 1 ng/L increase in troponin was associated with an average increase in LV mass of 0.53 g/m2 (β-coefficient 0.53; 95%CI: 0.29 to 0.77; p< 0.001 – Figure). Similarly, each 1 ng/L increase in troponin was associated with a 7% increase in the odds of LGE (OR 1.07; 95%CI: 1.02 to 1.13; p=0.009).
Conclusion: Among patients with Fabry’s disease, macrotroponins were detected for 1 in 9 patients. Correcting for macrotroponins increases the specificity of the association between troponin and LV mass or the presence of LGE.
