Dilated cardiomyopathy (DCM), the third most common cause of heart failure and the leading cause for heart transplantation (HTX), may be familial/genetic, viral and/or immune-mediated. Experimental and clinical data indicate that in a large proportion of patients myocarditis and DCM represent the acute and subacute/chronic stages of an organ-specific cardiac autoimmune disease, occurring in genetically predisposed subjects, with or without a recognized viral trigger. Serum anti-heart autoantibodies (AHA), directed against multiple antigens, are found in patients and family members and in about 60% of familial and nonfamilial pedigrees. AHA in myocarditis/DCM may be directed against mitochondrial proteins, cardiac myosin heavy chain, cardiac b1-adrenergic receptors, muscarinergic receptors, the sarcolemmal Na-K-ATPase, cardiac troponin I (cTNI), and other yet unknown targets. AHA predict DCM development among relatives, years before disease onset. Some AHA, being associated with phases of activation/relapse of the autoimmune process, provide negative prognostic markers. In addition AHA against the ADP/ATP carrier, cardiac myosin, cardiac b1-adrenergic receptors, and cTNI, as well as the cardio-depressive AHA, have been shown to possess functional effects on cardiac myocytes in vitro, in animals and possibly in a DCM subset, responsive to extracorporeal immunoadsorption (IA). This is the rationale for the clinical application of IA in an ongoing double-blind randomized multicenter trial in end-stage DCM (ClinicalTrials.gov identifier: NCT00558584). Another ongoing international prospective study aims at providing us with more information about the frequency, disease-specificity for inflammatory cardiomyopathy of multiple AHA types,and their potential role as prognostic markers either alone or in combinations. However, IA is expensive and invasive and only a subset of patients shows a benefit in terms of clinical and functional parameters at follow-up. Therefore, it is key to identify non-invasive predictors of clinical response to IA.
Ameling et al. provide an important proof-of concept study. In fact the combination of genetic expression profiles from EMB and the presence of serum autoantibodies with functional effects in terms of negative inotropism in isolated cardiomyocytes was the most powerful predictor of response to IA compared to the genetic markers and the immune markers alone. These findings are in keeping with what is seen in other autoimmune diseases, where the association of genetic markers, e.g. predisposing HLA haplotypes or gene expression profiles, and specific serum autoantibody types, provides the basis of risk stratification in affected patients and of disease prediction in first-degree relatives and other symptom-free individuals at risk. In addition, it supports the view that etiology-directed diagnosis, with integration of invasive tools, such as EMB using state-of the art criteria, and non-invasive etiology-specific markers, such as AHA, is key for providing personalized new therapy in DCM as well as optimization of financial resources.
Ameling et al. provide an important proof-of concept study. In fact the combination of genetic expression profiles from EMB and the presence of serum autoantibodies with functional effects in terms of negative inotropism in isolated cardiomyocytes was the most powerful predictor of response to IA compared to the genetic markers and the immune markers alone. These findings are in keeping with what is seen in other autoimmune diseases, where the association of genetic markers, e.g. predisposing HLA haplotypes or gene expression profiles, and specific serum autoantibody types, provides the basis of risk stratification in affected patients and of disease prediction in first-degree relatives and other symptom-free individuals at risk. In addition, it supports the view that etiology-directed diagnosis, with integration of invasive tools, such as EMB using state-of the art criteria, and non-invasive etiology-specific markers, such as AHA, is key for providing personalized new therapy in DCM as well as optimization of financial resources.
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