Key result
The integration of negative inotropic activity scores and expression levels of four genes accurately discriminated responders from non-responders to IA/IgG therapy (sensitivity 100%, specificity 100%).
Why the study?
Does combined assessment of negative inotropic activity and gene expression predict LVEF improvement in patients with dilated cardiomyopathy undergoing immunoadsorption therapy?
Observational (n=48)
Does combined assessment of negative inotropic activity and gene expression predict LVEF improvement in patients with dilated cardiomyopathy undergoing immunoadsorption therapy?
Effect estimate: Sensitivity 100% (95% CI 85.8-100)
Combined assessment of negative inotropic activity of antibodies and myocardial gene expression patterns can accurately predict which patients with dilated cardiomyopathy will respond to immunoadsorption therapy.
May enable prediction of IA/IgG response; leaves open clinical utility pending larger validation studies.
AIMS: Immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) represents a novel therapeutic approach in the treatment of dilated cardiomyopathy (DCM) which leads to the improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical, and molecular parameters for the prediction of the response of patients with DCM to IA/IgG. METHODS AND RESULTS: Forty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In eight patients with normal LVEF (controls), EMBs were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes, and gene expression profiles of EMBs were analysed. Dilated cardiomyopathy patients displaying improvement of LVEF (≥20 relative and ≥5% absolute) 6 months after IA/IgG were considered responders. Compared with non-responders (n = 16), responders (n = 24) displayed shorter disease duration (P = 0.006), smaller LV internal diameter in diastole (P = 0.019), and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin-proteasome pathway. The integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (BL) [sensitivity of 100% (95% CI 85.8-100%); specificity up to 100% (95% CI 79.4-100%); cut-off value: -0.28] and was superior to scores derived from antibodies, gene expression, or clinical parameters only. CONCLUSION: Combined assessment of NIA of antibodies and gene expression patterns of DCM patients at BL predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this therapeutic intervention.
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Ameling et al. (2012) conducted an observational in Dilated cardiomyopathy (n=48). Integration of negative inotropic activity scores and expression levels of four genes vs. Scores derived from antibodies, gene expression, or clinical parameters only was evaluated on Discrimination of responders from non-responders to IA/IgG therapy (improvement of LVEF ≥20 relative and ≥5% absolute) (Sensitivity 100%, 95% CI 85.8-100). The integration of negative inotropic activity scores and expression levels of four genes accurately discriminated responders from non-responders to IA/IgG therapy (sensitivity 100%, specificity 100%).
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