Long-term benefits of immunoadsorption in β(1)-adrenoceptor autoantibody-positive transplant candidates with dilated cardiomyopathy.
OBJECTIVE
Prolongation 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 β(1)-adrenoreceptor-autoantibodies (β(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 β(1)-AAB removal on IA results.


RESULTS
In a single-centre retrospective study of prospectively gathered information we evaluated all β(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 β(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 β(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 β(1)-AAB-positive DCM patients who underwent unspecific IA reached 69.4 ± 4.4% and was significantly higher (P < 0.05) than for both β(1)-AAB-positive DCM patients without IA (25.4 ± 11.4%) and β(1)-AAB-negative DCM patients who also underwent IA (47.4 ± 11.5). In patients with high β(1)-AAB levels, unspecific and specific IA showed the same high efficiency in β(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 β(1)-AAB reappearance, redetection of AABs coincided with worsening of cardiac function.


CONCLUSIONS
Removal of β(1)-AABs by specific or unspecific IA can improve cardiac function allowing long-term stability in end-stage DCM, which can spare many patients from HTx or will delay HTx listing for years. In β(1)-AAB-positive DCM patients the benefits of IA appeared to be associated with the removal of these antibodies.
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, D-13353, Germany. dandel@dhzb.de
Michael
M
Dandel
Gerd
G
Wallukat
Angela
A
Englert
Hans B
HB
Lehmkuhl
Christoph
C
Knosalla
Roland
R
Hetzer
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007163:Immunosorbent Techniques; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D014850:Waiting Lists
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001323:Autoantibodies; D002316:Cardiotonic Agents; D004232:Diuretics; D018342:Receptors, Adrenergic, beta-1; D004077:Digoxin