TNFα in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device

Background: In the heart elevated levels of TNF alpha can cause lethal heart failure, like Dilated Cardiomyopathy (DCM). The level of TNF alpha production is in part determined by promoter gene polymorphisms. We investigated whether the TNF alpha. promoter gene polymorphism is in this way involved in the outcome of end-stage heart failure and predicts whether patients require left ventricular assist device (LVAD) support or can be kept on medical therapy (MT)while awaiting heart transplantation (HTx). As most patients in this study received a heart transplant, the role of the TNF alpha polymorphisms in transplant rejection was studied as well. Methods and results: In twenty nine patients with DCM, 35 patients with Ischemic Heart Disease (IHD; both on MT), 26 patients on LVAD support and 61 cardiac transplant donors TNF alpha plasma level was detected by EASIA. In both patients groups high levels of TNF alpha plasma levels was observed however, in patients supported by LVAD this increase was much higher compared to patients on MT. Furthermore, this increase seems to be associated with the TNF1 allele ('G' at position -308) instead of the TNF2 allele (A at position -308). The promoter polymorphisms at positions -238, -244 and -308 were observed by polymerase chain reaction and sequencing. Polymorphism at positions -238, -244 and -308 did not show any relevant differences between the groups. However, at position -308, a trend of a higher incidence of the TNF2 allele (an "A" at position -308) in DCM patients compared to donors was shown. The distribution of the TNF1 and TNF2 alleles was not different in patients on medical therapy compared to the patients supported by a LVAD. No association was found between patients' TNF alpha promoter gene polymorphism and rejection. However, patients that received a donor heart with the TNF2 allele developed more rejection episodes, compared to patients that received a donor heart with the TNF1 allele. Conclusion: TNF alpha levels are high in patients with end-stage heart failure on MT, but even higher in patients on LVAD support. These high TNF alpha plasma levels however, are not correlated with the TNF2 allele but seems to be associated with the TNF1 allele. Furthermore, in HTx the donor TNF alpha gene seem to play a more important role in severity of acute rejection than that of the patient. (c) 2008 Elsevier B.V. All rights reserved.