This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Staudt, A. Articles by Felix, S. B. Search for Related Content PubMed PubMed Citation Articles by Staudt, A. Articles by Felix, S. B.

HEART FAILURE

Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy

Alexander Staudt, MD^*,*, Yvonne Staudt, MD^*, Marcus Dörr, MD^*, Marco Böhm, MD, Fabian Knebel, MD, Astrid Hummel, MD^*, Lydia Wunderle, MD^*, Malte Tiburcy, MD^*, Klaus D. Wernecke, PhD, Gert Baumann, MD and Stephan B. Felix, MD^*

^* Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
Medizinische Klinik I, Charité, Humboldt-Universität, Berlin, Germany
Institut für Medizinische Biometrie, Charité, Humboldt-Universität, Berlin, Germany

Manuscript received July 30, 2003; revised manuscript received April 16, 2004, accepted April 27, 2004.

^* Reprint requests and correspondence: Dr. Alexander Staudt, Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Fr.-Loefflerstr. 23a, D-17487 Greifswald, Germany (Email: staudt{at}mail.uni-greifswald.de).

OBJECTIVES: This research was conducted to evaluate the role played by the humoral immune system in cardiac dysfunction among dilated cardiomyopathy (DCM) patients, as enabled by immunoadsorption therapy (IA) that effectively removes functionally active cardiac autoantibodies from plasma.

BACKGROUND: Various circulating autoantibodies have been detected among patients suffering from DCM.

METHODS: Before IA, antibodies were purified from plasma of 45 DCM patients (left ventricular ejection fraction [LVEF] <30%). We analyzed the functional effects of antibodies (300 mg/l) on calcium transients and on systolic cell shortening in adult rat cardiomyocytes. After this in vitro analysis, IA was performed in four courses at one-month intervals until month 3.

RESULTS: Antibodies from 29 patients induced a reduction (>10%) in calcium transients (mean reduction: –16.5 ± 1.9%) and a simultaneous reduction (>10%) of cell shortening (mean reduction: –21.2 ± 1.8%) on cardiomyocytes (p < 0.001) (cardiodepressant group). Antibodies from 16 patients did not significantly influence calcium transients and cell shortening (<10%) (non-cardiodepressant group). During the first IA course, the cardiodepressant group demonstrated an acuteincrease in cardiac index (CI) from 2.2 ± 0.1 l/min/m² to 2.9 ± 0.1 l/min/m² (p < 0.001). In the non-cardiodepressant group, hemodynamics did not significantly change throughout three months. After three months before the final IA course (prolonged effects), the CI was 2.1 ± 0.1 l/min/m² in the non-cardiodepressant group and 2.9 ± 0.1 l/min/m² in the cardiodepressant group (p < 0.001). After three months LVEF increased only in the cardiodepressant group: from 20.8 ± 1% to 30.5 ± 1% (p < 0.01).

CONCLUSIONS: In the majority of DCM patients, disturbances of humoral immunity with production of cardiodepressant antibodies may play a functional role in cardiac dysfunction. Evidence of cardiodepressant antibodies predicts hemodynamic benefits during IA.

Abbreviations and Acronyms   CI = cardiac index   DCM = dilated cardiomyopathy   HF = heart failure   IA = immunoadsorption   Ig = immunoglobulin   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   LVIDd = left ventricular internal diameter in diastole   NYHA = New York Heart Association   SVI = stroke volume index   SVR = systemic vascular resistance

This article has been cited by other articles:

				M. Noutsias, S. Pankuweit, and B. Maisch Chapter 56 Myocarditis, cardiac tamponade, and pericarditis The ESC Textbook of Acute and Intensive Cardiac Care, December 1, 2010; 1(1): med-9780199584314-chapter - med-9780199584314-chapter. [Abstract] [Full Text] [PDF]

				S. Heymans, E. Hirsch, S. D. Anker, P. Aukrust, J.-L. Balligand, J. W. Cohen-Tervaert, H. Drexler, G. Filippatos, S. B. Felix, L. Gullestad, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology Eur J Heart Fail, February 1, 2009; 11(2): 119 - 129. [Abstract] [Full Text] [PDF]

				O. M. Hess, W. McKenna, and H.-P. Schultheiss CHAPTER 18 Myocardial Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				A. Staudt, P. Eichler, C. Trimpert, S. B. Felix, and A. Greinacher Fc{gamma} Receptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1684 - 1692. [Abstract] [Full Text] [PDF]

				S. Goser, M. Andrassy, S. J. Buss, F. Leuschner, C. H. Volz, R. Ottl;, S. Zittrich;, N. Blaudeck, S. E. Hardt, G. Pfitzer, et al. Cardiac Troponin I but Not Cardiac Troponin T Induces Severe Autoimmune Inflammation in the Myocardium Circulation, October 17, 2006; 114(16): 1693 - 1702. [Abstract] [Full Text] [PDF]

				F. De Cobelli, M. Pieroni, A. Esposito, C. Chimenti, E. Belloni, R. Mellone, T. Canu, G. Perseghin, C. Gaudio, A. Maseri, et al. Delayed Gadolinium-Enhanced Cardiac Magnetic Resonance in Patients With Chronic Myocarditis Presenting With Heart Failure or Recurrent Arrhythmias J. Am. Coll. Cardiol., April 18, 2006; 47(8): 1649 - 1654. [Abstract] [Full Text] [PDF]