Activated nuclear transcription factor κB in patients with myocarditis and dilated cardiomyopathy—relation to inflammation and cardiac function

Objectives and backgroundMyocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-κB (NFκB).MethodsA total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NFκB was performed.ResultsNFκB was increased in patients with myocarditis when compared with controls (11.1 ± 7.1% vs. 5.0 ± 5.3%, P < 0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NFκB when compared with reduced function (r2 = 0.72, P < 0.001). In parallel, inverse correlation of NFκB and left ventricular enddiasstolic volume was found (r2 = 0.43, P < 0.02). Increased activated NFκB was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NFκB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFκB activation.ConclusionsIncreased activation of NFκB is related to inflammatory processes in myocarditis. Since activated NFκB correlates with left ventricular function, it could be assumed that NFκB activation occurs at early stages of inflammation. Potentially, NFκB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFκB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed.