Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column-A prospective, multicenter, randomized, within-patient and parallel-group comparative study to evaluate efficacy and safety

Abstract

Over the past few decades, several cardiac autoantibodies have been reported in sera from patients with dilated cardiomyopathy (DCM). Immunoadsorption (IA) therapy is one of the therapeutic tools to remove such autoantibodies. The objective of this study was to investigate functional effects of IA therapy using a tryptophan column in severe DCM patients. Of 49 patients enrolled, 44 were randomized from 10 sites in Japan. IA therapy was conducted in 40 patients with DCM (refractory to standard therapy for heart failure, New York Heart Association [NYHA] class III/IV, left ventricular ejection fraction [LVEF] <30%). Mean echocardiographic LVEF was significantly improved (23.8 ± 1.3% to 25.9 ± 1.3%, P = 0.0015). However, mean radionuclide LVEF over 3 months of IA therapy was not significantly improved (20.8 ± 1.1% to 21.9 ± 1%, P = 0.0605). The cardiothoracic ratio was also significantly decreased (P = 0.0010). NYHA functional class (P < 0.0001), subjective symptoms assessed by a quality of life questionnaire (P = 0.0022), maximum oxygen consumption (P = 0.0074), and 6-minute walk distance (P = 0.0050) were improved after IA therapy. Subgroup analysis revealed improvement of echocardiographic LVEF in patients with higher baseline autoantibody scores but not in those with lower scores. IA therapy improved subjective symptoms and exercise capacity in patients with refractory heart failure resulting from DCM. Favorable effect on cardiac function was noted in patients with higher autoantibody scores. J. Clin. Apheresis 31:535-544, 2016. © 2015 Wiley Periodicals, Inc.

Keywords: antibodies; dilated cardiomyopathy; heart failure; immune system.

Figure 1

Study protocol. RI, radionuclide ventriculography; UCG, ultrasonic echocardiography

Figure 2

Randomization and allocation of the study subjects. 1) Patients withdrew consent, n = 1; physicians judged to exclude, n = 4. 2) Physicians discontinued because of adverse events, n = 3; patients withdrew consent, n = 2; physicians judged to discontinue IA, n = 1; withdrew because of cardiac event, n = 1. 3) Patients discontinued IA, n = 2; Patients withdrew consent, n = 2.

Figure 3

Baseline autoantibody concentrations. Left panel, total IgG antibodies; right panel, IgG3 subclass antibodies.

Figure 4

Changes in cardiac function before and 3 months (3M) after immunoadsorption (IA) therapy according to the baseline autoantibody score. *P < 0.05. (A) Left ventricular ejection fraction (LVEF); (B) left ventricular end‐systolic volume (LVESV).