Objectives and background: Myocarditis 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-kappa B (NF kappa B). Methods: A 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 NF kappa B was performed. Results: NF kappa B 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 NF kappa B when compared with reduced function (r(2) = 0.72, P < 0.001). In parallel, inverse correlation of NF kappa B and left ventricular enddiasstolic volume was found (r(2) = 0.43, P < 0.02). Increased activated NF kappa B was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NF kappa B activation was seen in cytomegalovirus persistence. Parvovirus 1319 persistence did not affect NF kappa B activation. Conclusions: Increased activation of NF kappa B is related to inflammatory processes in myocarditis. Since activated NF kappa B correlates with left ventricular function, it could be assumed that NF kappa B activation occurs at early stages of inflammation. Potentially, NF kappa B could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NF kappa B is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed. (c) 2005 Elsevier Inc. All rights reserved.