Long‐term benefits of immunoadsorption in β₁‐adrenoceptor autoantibody‐positive transplant candidates with dilated cardiomyopathy

Abstract

AimsProlongation of waiting times for heart transplantation (HTx) increases the need for new therapies. In short-term follow-up studies, immunoadsorption (IA) appeared beneficial in dilated cardiomyopathy (DCM) associated with b 1 -adrenoreceptor-autoantibodies (b 1 -AABs). This study aimed to investigate the long-term benefits of IA in HTx candidates with DCM, patients' responsiveness to IA, and the impact of b 1 -AAB removal on IA results. Methods and resultsIn a single-centre retrospective study of prospectively gathered information we evaluated all b 1 -AAB-positive and -negative HTx candidates with end-stage DCM [left ventricular ejection fraction (LVEF) ,30%] who underwent IA between 1995 and 2005 (follow-up thereafter: 5.3 -14.7 years). As controls we used all b 1 -AAB-positive DCM patients referred for HTx during the same time period who received no IA therapy. We also looked for differences in efficacy between unspecific IA (unselective antibody removal) and specific IA (selective b 1 -AAB removal). The main outcome measures were cardiac function and HTx/ventricular assist device (VAD)-free patient survival. The probability for 5-year HTx/VAD-free survival for the108 b 1 -AAB-positive DCM patients who underwent unspecific IA reached 69.4 + 4.4% and was significantly higher (P , 0.05) than for both b 1 -AAB-positive DCM patients without IA (25.4 + 11.4%) and b 1 -AAB-negative DCM patients who also underwent IA (47.4 + 11.5). In patients with high b 1 -AAB levels, unspecific and specific IA showed the same high efficiency in b 1 -AAB removal. LVEF and New York Heart Assocation class improved (P , 0.01) after both, but without differences in improvement after specific or unspecific IA. The prevalence of responders to specific and unspecific IA was similar (78.3% vs. 79.6%). In 76% of the patients with b 1 -AAB reappearance, redetection of AABs coincided with worsening of cardiac function. ConclusionsRemoval of b 1 -AABs by specific or unspecific IA can improve cardiac function allowing long-term stability in endstage DCM, which can spare many patients from HTx or will delay HTx listing for years. In b 1 -AAB-positive DCM patients the benefits of IA appeared to be associated with the removal of these antibodies.--

Immunoadsorption can improve cardiac function in transplant candidates with non-ischemic dilated cardiomyopathy associated with diabetes mellitus

“…Short-and long-term results of unspecific IA were also better in b 1 -AAB positive than b 1 -AAB negative patients [13,20]. Today IA is accepted as a therapy option for idiopathic DCM [21].…”

“…Thereafter, a large number of studies evaluating the short-term ( 1 year) efficacy of IA in idiopathic DCM showed significant improvement in LV ejection fraction (LVEF) and/or cardiac index for both unselective IgG removal and selective b 1 -AAB removal [9,15e19]. A large recently published long-term follow-up study also showed that b 1 -AAB removal by both specific and unspecific immunoadsorption (IA) can improve heart function in more than 70% of patients with end-stage idiopathic DCM, allowing long-term cardiac stability with a 5-year survival probability of more than 69% without the necessity of HTx or mechanical circulatory support [13].…”

Use of Biomarkers for the Prediction of Treatment Response: Immunoadsorption in Dilated Cardiomyopathy as a Clinical Example

“…Two studies have also shown long-term effects of IA with respect to the improvement of cardiac function, morphology, and the symptom state (Dandel et al 2012;Müller et al 2000). In addition, one of these studies could demonstrate that IA may also be associated with reduced rates of heart transplantation and the need for (artificial) ventricular assist devices during a follow-up time of up to 14.7 years (Dandel et al 2012). However, all these studies were either uncontrolled or open controlled studies which compared the effects of IA to conventional therapy but without any sham intervention in the control group.…”

“…Thus, currently available data have demonstrated that IA/IgG resulted in significant increase in cardiac functional and morphological parameters, symptoms' relief, heart failure related clinical biomarkers (Dörffel et al 1997;Felix et al 2000;Müller et al 2000;Felix et al 2002;Staudt et al 2002Staudt et al , 2005Staudt et al , 2006Staudt et al , 2010Doesch et al 2010;Pokrovsky et al 2013), increased exercise tolerance , and improvement of endothelial function (Bulut et al 2011). Two studies have also shown long-term effects of IA with respect to the improvement of cardiac function, morphology, and the symptom state (Dandel et al 2012;Müller et al 2000). In addition, one of these studies could demonstrate that IA may also be associated with reduced rates of heart transplantation and the need for (artificial) ventricular assist devices during a follow-up time of up to 14.7 years (Dandel et al 2012).…”

Chronic Chagas disease: from basics to laboratory medicine

“…In this context, the elimination of pathogenetic AABs, such as the pathogenic β 1-AABs, via apheresis techniques has been suggested for Chagas heart disease [90] . The idea of using apheresis in the treatment of Chagas heart disease is supported by the well-documented benefits of β -1-AAB immunoadsorption in patients with DCM [91] .…”