Estudio de biomarcadores predictores de miocardiopatías en pacientes genotipados

Abstract

HYPOTHESIS Cardiomyopathies are diseases of the heart muscle. Their main clinical characteristics are ventricular dilatation, hypertrophy, and cardiac arrhythmia, often followed by heart failure and sudden cardiac death. Generally, early differential diagnosis is key for myocardiopathies, but when they affect pathogenic mutations carriers without cardiomyopathies, a regular clinical follow-up is critical. Until now, anamnesis, clinical evaluation, and imaging techniques have been the main tools to predict the development of the disease, but these are very limited when it comes to predicting the onset of the disease. New diagnostic techniques such as serum biomarkers could provide with key additional information for presymptomatic stages of cardiomyopathies as well as help to diagnose and stratify them easily and reliably. Currently, however, there is no such biomarker. GOALS 1) To study the values of the analysed biomarkers, comparing their values in affected carriers, unaffected carriers, and a control group of healthy non-carriers for each of the three cardiomyopathies. 2) To analyse the use of the studied biomarkers in order to identify subclinical disease in unaffected carriers with pathogenic mutations in the three diseases. 3) To determine the severity of the disease based on the concentrations of the different biomarkers. 4) To connect the concentration of the different biomarkers to functional capacity according to the NYHA scale in each of the three diseases. 5) To study the possible association of biomarkers with cardiomyopathies’ clinical variables. METHODOLOGY A cross-sectional observational study has been conducted with patients that were prospectively evaluated at the inherited cardiomyopathies consultation at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) in Murcia, from 2005 to 2013. These patients were diagnosed with familial cardiomyopathy. Samples were studied at the Genetic Diagnosis Laboratory which is part of the Clinical Analysis Department of the HCUVA, Murcia. CONCLUSIONS 1) There is a connection between the different medical conditions (affected, unaffected carrier, and healthy) in genetic cardiomyopathies and inflammation, fibrosis, left ventricular wall stress, and cell damage biomarkers. 2) In arrhythmogenic cardiomyopathy, biomarkers with diagnostic value in preclinical stages are markers of inflammation IL-6, CT-1, and the CT-1/SOCS3 ratio. 3) In dilated cardiomyopathy, the biomarker with diagnostic value in preclinical stages is the cell damage marker TnThs. 4) In hypertrophic cardiomyopathy, the biomarkers with diagnostic value in preclinical stages are SOCS3 as marker of inflammation and TnThs as a cell damage marker. 5) In arrhythmogenic cardiomyopathy, the biomarkers associated with severity are IL-6, SOCS3 and the CT-1/SOCS3 ratio as markers of inflammation, NT-proBNP and ST2 as markers of left ventricular wall stress, TnThs as markers of cell damage, and CICP, PINP and the CICP/NTX ratio as markers of fibrosis. 6) In dilated cardiomyopathy, the biomarkers associated with severity are IL-6 as a marker of inflammation, NT-proBNP as a marker of left ventricular wall stress, TnThs as a marker of cell damage, and the CICP/NTX ratio as a marker of fibrosis. 7) In hypertrophic cardiomyopathy, the biomarkers associated with severity are IL-6 and the CT-1/SOCS3 ratio as markers of inflammation, NT-proBNP as a marker of left ventricular wall stress and TnThs as a marker of cell damage. 8) In dilated cardiomyopathy, the biomarker related to worse functional capacity according to the NYHA classification is the TnThs cell damage marker. 9) In hypertrophic cardiomyopathy, the biomarkers related to worse functional capacity according to the NYHA classification are the NT-proBNP left ventricular wall stress marker and the TnThs cell damage marker. 10) The NT-proBNP left ventricular wall stress biomarker is the biomarker associated with the greatest number of clinical variables in arrhythmogenic, dilated, and hypertrophic cardiomyopathy